Lymphoma
Conditions
Brief summary
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.
Interventions
DRUGBendamustine
Bendamustine 90 milligrams per meter-squared (mg/m\^2) per day administered IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
DRUGObinutuzumab
Obinutuzumab 1000 milligrams (mg) IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
DRUGPolatuzumab vedotin (Liquid)
Polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) administered IV on Day 2 of Cycle 1, then on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
DRUGRituximab
Rituximab standard dose, 375 mg/m\^2 IV on Day 1 of each cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
DRUGPolatuzumab vedotin (Lyophilized)
Participants in the New Formulation (NF) Cohort (Arms G and H) will follow the same schedule and dosing requirements as participants in the other Phase II cohorts (Arms A-F).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL * If the participant has received prior bendamustine, response duration must have been greater than (\>) 1 year (for participants who have relapse disease after a prior regimen) * At least one bi-dimensionally measurable lesion on imaging scan defined as \>1.5 centimeters (cm) in its longest dimension * Confirmed availability of archival or freshly collected tumor tissue * The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review. * Life expectancy of at least 24 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Adequate hematological function unless inadequate function is due to underlying disease
Exclusion criteria
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs, or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products * Contraindication to bendamustine, rituximab, or obinutuzumab * Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives before Cycle 1 Day 1 * Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1 * Ongoing corticosteroid use \>30 mg per day prednisone or equivalent, for purposes other than lymphoma symptom control * Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1 Day 1 * Prior allogeneic SCT * Eligibility for autologous SCT * Grade 3b FL * History of transformation of indolent disease to DLBCL * Primary or secondary CNS lymphoma * Current Grade \>1 peripheral neuropathy * Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm) * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1 Day 1 * Suspected or latent tuberculosis * Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C virus (HCV) antibody * Known history of human immunodeficiency virus (HIV) seropositive status or known infection with human T-cell leukemia virus 1 (HTLV-1) virus * Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort * Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation function tests * Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle 1, Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Percentage of Participants With Adverse Events (AEs) | From the study start up to the end of the study (up to approximately 84 months) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). |
| Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs | From Month 37 to Month 84 (up to approximately 47 months) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. |
| Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin | Baseline up to approximately Month 24 | The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number. |
| Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline up to approximately Month 24 | The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number. |
| Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized) | From Month 37 to Month 84 (up to approximately 47 months) | The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number. |
| Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC) | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. |
| Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks) | CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. |
| Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks | Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms\*day per milliliters. |
| Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg) |
| Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). |
| Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months) | BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN & ELS, score=4 or 5, reduced UT than baseline (BL) & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions. |
| DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC | Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months) | BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN & ELS, score=4 or 5, reduced UT than baseline (BL) & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions. |
| DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator | From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months) | DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions. |
| DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC | From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months) | DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions. |
| DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator | From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months) | PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H. |
| DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC | From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months) | PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H. |
| Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks) | CR was assessed by Investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. |
| Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately\>liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). |
| Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). |
| Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). |
| Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator | Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months]) | BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes & ELS, score=4 or 5, reduced UT than BL & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions. |
| Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC | Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months]) | BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes & ELS, score=4 or 5, reduced UT than BL & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions. |
| Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator | From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months]) | DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions. |
| Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months) | PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. |
| Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose | PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H. |
| Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC | From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months]) | DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions. |
| Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator | From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months]) | PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H. |
| Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC | From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months]) | PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H. |
| Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator | From Month 37 to Month 84 (up to approximately 47 months) | EFS was defined as time from randomization to disease progression or relapse, as assessed by the investigator or death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H. |
| Phase II NF Cohorts: Overall Survival (OS) | From Month 37 to Month 84 (up to approximately 47 months) | OS was defined as the time from the date of randomization or first treatment (for obinutuzumab arms) to the date of death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H. |
| Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks) | CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. |
| Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks) | CR was determined by Investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number. |
| Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks) | CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number. |
| Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). |
| Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose | PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H. |
| Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months) | PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. |
| Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose | PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H. |
| Plasma Concentration of Bendamustine | Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose | Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H). |
| Serum Concentration of Rituximab | Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months) | Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H). |
| Serum Concentration of Obinutuzumab | Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months) | Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. |
| Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody and unconjugated MMAE were measured. |
| Phase II: Cmax of Bendamustine and Rituximab in Arms B and D | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | — |
| Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured. |
| Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: Percentage of Participants With AEs | From the study start up to the end of the study (up to approximately 84 months) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. |
| Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | — |
| Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks | PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: CL of Bendamustine and Rituximab in Arms B and D | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | — |
| Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Phase II: Vss of Bendamustine and Rituximab in Arms B and D | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | — |
| Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized) | Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. |
| Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall) | The TINAS is an 11-item questionnaire that assesses the severity of neuropathy-related symptoms in the last 24 hours. The 11 items assessed were: hot/burning sensations in hands/feet, sensations pins and needles arms/legs, numbness or tingling in hands/feet, sensations of electric shock, pain when touching cold things, cramps in hands/feet, discomfort when touching things, discomfort skin contact with something, trouble grasping small objects, trouble walking loss feeling legs/feet, difficulty balance loss feeling leg/feet. Each item was scored on a 0-10 scale, with 0 being the symptom is not present, and 10 being the symptom is as bad as the participant can imagine. Higher scores indicate more severe disease. Scores were averaged at each week. |
| Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) | PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day\*micrograms per milliliter \[day\*ug/mL\]). |
| Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin | Baseline to approximately Month 24 | The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number. |
| Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline to approximately Month 24 | The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number. |
| Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | CR was assessed by investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. |
| Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number. |
| Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months) | PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. |
| Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). |
| Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. Bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). |
| Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | CR was determined by investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimetres (cm) in in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. |
| Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | CR was determined by IRC a at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number. |
| Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks) | OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). |
Countries
Australia, Canada, Czechia, France, Germany, Hungary, Italy, Netherlands, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 331 participants with relapsed or refractory (R/R) follicular lymphoma (FL) or diffuse large B cell lymphoma (DLBCL) were enrolled in this study at 56 investigative sites in the following countries: Australia, Canada, Czech Republic, France, Germany, Hungary, Italy, Korea, the Netherlands, Spain, Turkey, United Kingdom, and the United States from 15 October 2014 to 21 October 2021.
Pre-assignment details
Participants were enrolled in Phase Ib and Phase II to receive polatuzumab vedotin (pola) (liquid formulation in randomized & expansion stages; lyophilized formulation in new formulation (NF) cohorts) in combination with standard doses of bendamustine (B) & rituximab (R)/obinutuzumab (G). Out of 331 participants, 327 participants received at least one dose of study drug and their intended treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola. | 6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola. | 6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and obinutuzumab 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 in combination with pola. | 6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and obinutuzumab 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 in combination with pola. | 6 |
| Arm A (Phase II Randomization): Pola+BR in FL Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola. | 39 |
| Arm B (Phase II Randomization): BR in FL Participants with FL received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1 (each cycle is 28 days), thereafter on Days 1 and 2 of Cycles 2 to 6 in combination with rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1 to 6. | 41 |
| Arm C (Phase II Randomization): Pola+BR in DLBCL Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola. | 40 |
| Arm D (Phase II Randomization): BR in DLBCL Participants with DLBCL received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1 (each cycle is 21 days), thereafter on Days 1 and 2 of Cycles 2 to 6 in combination with rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1 to 6. | 40 |
| Arm E (Phase II Expansion): Pola+BG in FL Participants with FL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 28 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and obinutuzumab 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 in combination with pola. | 20 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL Participants with DLBCL received pola, 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and obinutuzumab 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 in combination with pola. | 21 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL Participants with DLBCL received pola (lyophilized formulation), 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 (each cycle is 21 days), and thereafter on Day 1 of Cycles 2 to 6. Participants also received bendamustine 90 mg/m\^2, as IV infusion on Days 2 and 3 of Cycle 1, and thereafter on Days 1 and 2 of Cycles 2 to 6 and rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1 to 6, in combination with pola. | 106 |
| Total | 331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Death | 2 | 2 | 2 | 4 | 15 | 11 | 26 | 30 | 2 | 18 | 65 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Not treated/Per Sponsor Participant Could not Continue/Pathology Showed Transformation: Cycle 1Day 1 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 0 | 0 | 6 | 6 | 6 | 1 | 1 | 10 |
Baseline characteristics
| Characteristic | Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Total | Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Arm F (Phase II Expansion): Pola+BG in DLBCL | Arm E (Phase II Expansion): Pola+BG in FL | Arm D (Phase II Randomization): BR in DLBCL | Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm C (Phase II Randomization): Pola+BR in DLBCL | Arm B (Phase II Randomization): BR in FL | Arm A (Phase II Randomization): Pola+BR in FL | Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.0 years | 67.0 years | 70.0 years | 65.0 years | 60.5 years | 71.0 years | 68.0 years | 67.0 years | 63.0 years | 65.0 years | 71.0 years | 63.5 years |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 14 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 6 Participants | 285 Participants | 87 Participants | 19 Participants | 16 Participants | 36 Participants | 6 Participants | 35 Participants | 34 Participants | 34 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Not Stated | 0 Participants | 22 Participants | 13 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 10 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 30 Participants | 8 Participants | 6 Participants | 1 Participants | 4 Participants | 1 Participants | 6 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 34 Participants | 14 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 5 Participants | 6 Participants | 4 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 259 Participants | 83 Participants | 15 Participants | 16 Participants | 31 Participants | 5 Participants | 26 Participants | 33 Participants | 33 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 151 Participants | 54 Participants | 10 Participants | 10 Participants | 15 Participants | 4 Participants | 12 Participants | 23 Participants | 18 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 180 Participants | 52 Participants | 11 Participants | 10 Participants | 25 Participants | 2 Participants | 28 Participants | 18 Participants | 21 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 6 | 2 / 6 | 2 / 6 | 4 / 6 | 16 / 39 | 11 / 41 | 26 / 40 | 30 / 40 | 3 / 20 | 18 / 21 | 65 / 106 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 38 / 38 | 39 / 41 | 36 / 39 | 37 / 39 | 20 / 20 | 19 / 20 | 103 / 106 |
| serious Total, serious adverse events | 2 / 6 | 4 / 6 | 4 / 6 | 5 / 6 | 25 / 38 | 12 / 41 | 24 / 39 | 27 / 39 | 8 / 20 | 13 / 20 | 57 / 106 |
Outcome results
Primary
Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
Population: Safety population consisted of all ITT participants from Arms G+H (Phase II NF Cohort) who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs | 99.1 percentage of participants |
Primary
Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms\*day per milliliters.
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Population: PK population included all ITT participants in Arm G (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' is the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized) | acMMAE | 2880 ng*day/mL | Geometric Coefficient of Variation 0.15 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized) | MMAE | 21.6 ng*day/mL | Geometric Coefficient of Variation 45 |
Primary
Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Population: PK evaluable population included all the ITT participants in Arm G (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' is the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized) | acMMAE | 724 nanograms per milliliters (ng/mL) | Geometric Coefficient of Variation 10 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized) | MMAE | 2.01 nanograms per milliliters (ng/mL) | Geometric Coefficient of Variation 38 |
Primary
Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Population: As pre-specified in the protocol the analysis of this OM was based on sponsor's discretion however, sponsor opted to not collect data for this OM.
Primary
Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Population: As pre-specified in the protocol the analysis of this outcome measure (OM) was based on sponsor's discretion however, sponsor opted to not collect data for this OM.
Primary
Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Time frame: 6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Population: ITT population included all randomized participants in Arm H (Phase II NF Cohort) irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 42.2 percentage of participants |
Primary
Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
Population: Safety population consisted of all ITT participants from Arm G+H (Phase II NF cohort) who received at least one dose of study medication. 'Overall Number Analyzed' is the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized) | Baseline Prevalence of ADAs to Polatuzumab | 0.0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized) | Post-Baseline Incidence of ADAs to Polatuzumab | 2.6 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized) | Baseline Prevalence of ADAs to Polatuzumab | 1.6 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized) | Post-Baseline Incidence of ADAs to Polatuzumab | 5.0 percentage of participants |
Primary
Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Time frame: Baseline up to approximately Month 24
Population: Safety population consisted of all ITT participants from Cohort 1a (Phase Ib) who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin | Baseline Prevalence of ADAs | 50.0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin | Post-Baseline Incidence of ADAs | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin | Baseline Prevalence of ADAs | 33.3 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin | Post-Baseline Incidence of ADAs | 33.3 percentage of participants |
Primary
Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Time frame: Baseline up to approximately Month 24
Population: Safety population consisted of all ITT participants from Cohort 1b (Phase Ib) who received at least one dose of study medication. 'Number Analyzed' is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADAs to Polatuzumab vedotin | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Obinutuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADA to Obinutuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Polatuzumab vedotin | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Polatuzumab vedotin | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADAs to Polatuzumab vedotin | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADA to Obinutuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Obinutuzumab | 0 percentage of participants |
Primary
Phase Ib: Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
Time frame: From the study start up to the end of the study (up to approximately 84 months)
Population: Safety population consisted of all ITT participants from Phase Ib who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase Ib: Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase Ib: Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
Primary
Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)
CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II Randomized and NF cohorts irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC) | 69.2 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC) | 63.4 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC) | 42.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC) | 17.5 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC) | 39.6 percentage of participants |
p-value: 0.535395% CI: [-14.53, 25.38]Cochran-Mantel-Haenszel
p-value: 0.012895% CI: [4.89, 42.63]Cochran-Mantel-Haenszel
Secondary
Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Time frame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Population: PK evaluable population included all the ITT participants in Arm G+H (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Post Dose | 653 ng/mL | Standard Deviation 237 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 14.6 ng/mL | Standard Deviation 8.66 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Post Dose | 667 ng/mL | Standard Deviation 155 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 23.2 ng/mL | Standard Deviation 8.59 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Post Dose | 659 ng/mL | Standard Deviation 156 |
Secondary
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab
PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Time frame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Population: PK evaluable population included all the ITT participants in Arm G+H (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Post Dose | 33.9 ng/mL | Standard Deviation 11.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 3.27 ng/mL | Standard Deviation 4.37 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Post Dose | 36.0 ng/mL | Standard Deviation 8.71 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 5.41 ng/mL | Standard Deviation 1.79 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Post Dose | 39.2 ng/mL | Standard Deviation 7.3 |
Secondary
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Time frame: Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose
Population: PK evaluable population included all the ITT participants in Arm G (Phase II NF Cohort) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Post Dose | 0.590 ng/mL | Standard Deviation 1.08 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.229 ng/mL | Standard Deviation 0.248 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Post Dose | 0.316 ng/mL | Standard Deviation 0.213 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.186 ng/mL | Standard Deviation 0.118 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Post Dose | 0.256 ng/mL | Standard Deviation 0.118 |
Secondary
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
CR was determined by Investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Population: ITT population included all randomized participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 9.5 percentage of participants |
Secondary
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Population: ITT population included all randomized participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 14.3 percentage of participants |
Secondary
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Population: ITT population included all randomized participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 35.7 percentage of participants |
Secondary
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Population: ITT population included all randomized participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 38.1 percentage of participants |
Secondary
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Population: ITT population included all randomized participants in Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 33.3 percentage of participants |
Secondary
Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Population: As pre-specified in the protocol the analysis of this OM was based on sponsor's discretion however, sponsor opted to not collect data for this OM.
Secondary
Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Population: As pre-specified in the protocol the analysis of this OM was based on sponsor's discretion however, sponsor opted to not collect data for this OM.
Secondary
Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Population: As pre-specified in the protocol the analysis of this OM was based on sponsor's discretion however, sponsor opted to not collect data for this OM.
Secondary
Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Population: As pre-specified in the protocol the analysis of this OM was based on sponsor's discretion however, sponsor opted to not collect data for this OM.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized) | acMMAE | — |
| Unknown | Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized) | MMAE | — |
| Unknown | Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized) | Total Ab | — |
Secondary
Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin
The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Time frame: Baseline to approximately Month 24
Population: Safety population consisted of all ITT participants from Arms A and C (Phase II) who received at least one dose of study medication. 'Overall Number Analyzed' is the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin | Baseline Prevalence of ADAs | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin | Post-Baseline Incidence of ADAs | 7.9 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin | Baseline Prevalence of ADAs | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin | Post-Baseline Incidence of ADAs | 2.9 percentage of participants |
Secondary
Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have Treatment-induced ADAs or Treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Time frame: Baseline to approximately Month 24
Population: Safety population consisted of all ITT participants from Arms E and F (Phase II) who received at least one dose of study medication. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Polatuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADAs to Polatuzumab | 5.3 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADAs to Obinutuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Obinutuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADAs to Obinutuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Polatuzumab | 0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Post-Baseline Incidence of ADAs to Polatuzumab | 5.6 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab | Baseline Prevalence of ADAs to Obinutuzumab | 0 percentage of participants |
Secondary
DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
Population: ITT population included all randomized participants in DLBCL Cohorts irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. 'Overall Number Analyzed' are the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC | 10.908 months |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC | 10.645 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC | 25.758 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC | 13.437 months |
p-value: 0.245195% CI: [0.25, 1.43]Log Rank
Secondary
DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
Population: ITT population included all randomized participants in DLBCL Cohorts irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. 'Overall Number Analyzed' are the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator | 12.665 months |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator | 4.074 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator | 16.099 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator | 11.335 months |
p-value: 0.024595% CI: [0.19, 0.91]Log Rank
Secondary
DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC
BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN & ELS, score=4 or 5, reduced UT than baseline (BL) & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
Population: ITT population included all randomized participants in DLBCL Cohorts irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC | 62.5 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC | 25.0 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC | 42.9 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC | 57.5 percentage of participants |
p-value: 0.000595% CI: [15.82, 54.62]Cochran-Mantel-Haenszel
Secondary
DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC
PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
Population: ITT population included all randomized participants in DLBCL Cohorts irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC | 9.248 months |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC | 3.713 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC | 5.848 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC | 6.965 months |
p-value: 0.000395% CI: [0.23, 0.66]Log Rank
Secondary
DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator
PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
Population: ITT population included all randomized participants in DLBCL Cohorts irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator | 7.491 months |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator | 2.037 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator | 5.125 months |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator | 5.881 months |
p-value: <0.000195% CI: [0.2, 0.56]Log Rank
Secondary
Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day\*micrograms per milliliter \[day\*ug/mL\]).
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for bendamustine and rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE | 2830 day*ug/mL | Geometric Coefficient of Variation 12.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab | 298 day*ug/mL | Geometric Coefficient of Variation 4.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE | 2110 day*ug/mL | Geometric Coefficient of Variation 28.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab | 214 day*ug/mL | Geometric Coefficient of Variation 35.9 |
Secondary
Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for bendamustine and obinutuzumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE | 2600 day*ug/mL | Geometric Coefficient of Variation 34.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab | 267 day*ug/mL | Geometric Coefficient of Variation 30.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE | 2650 day*ug/mL | Geometric Coefficient of Variation 16.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab | 252 day*ug/mL | Geometric Coefficient of Variation 21.6 |
Secondary
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for bendamustine and obinutuzumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE | 12.3 mL/day/kg | Geometric Coefficient of Variation 34.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab | 6.76 mL/day/kg | Geometric Coefficient of Variation 30.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE | 12.1 mL/day/kg | Geometric Coefficient of Variation 17 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab | 7.17 mL/day/kg | Geometric Coefficient of Variation 22.2 |
Secondary
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for bendamustine and rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE | 11.3 mL/day/kg | Geometric Coefficient of Variation 12.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab | 6.05 mL/day/kg | Geometric Coefficient of Variation 4.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE | 15.2 mL/day/kg | Geometric Coefficient of Variation 27.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab | 8.48 mL/day/kg | Geometric Coefficient of Variation 35.2 |
Secondary
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Cmax was not evaluated for Bendamustine and Obinutuzumab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE: Cycle 4 | 749 ng/mL | Standard Deviation 158 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab: Cycle 2 | 45.0 ng/mL | Standard Deviation 12.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE: Cycle 2 | 816 ng/mL | Standard Deviation 168 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab: Cycle 4 | 44.2 ng/mL | Standard Deviation 11.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab: Cycle 1 | 38.7 ng/mL | Standard Deviation 9.84 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Unconjugated MMAE: Cycle 1 | 2.17 ng/mL | Standard Deviation 1.08 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE: Cycle 1 | 738 ng/mL | Standard Deviation 165 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Unconjugated MMAE: Cycle 1 | 2.39 ng/mL | Standard Deviation 0.492 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE: Cycle 1 | 725 ng/mL | Standard Deviation 104 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE: Cycle 2 | 841 ng/mL | Standard Deviation 115 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE: Cycle 4 | 721 ng/mL | Standard Deviation 97.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab: Cycle 1 | 34.9 ng/mL | Standard Deviation 7.52 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab: Cycle 2 | 43.1 ng/mL | Standard Deviation 9.52 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab: Cycle 4 | 48.2 ng/mL | Standard Deviation 12.5 |
Secondary
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Cmax was not evaluated for Bendamustine and Rituximab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE: Cycle 4 | 763 ng/mL | Standard Deviation 159 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab: Cycle 2 | 36.6 ng/mL | Standard Deviation 8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE: Cycle 2 | 697 ng/mL | Standard Deviation 129 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab: Cycle 4 | 41.3 ng/mL | Standard Deviation 9.98 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab: Cycle 1 | 34.3 ng/mL | Standard Deviation 8.57 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Unconjugated MMAE: Cycle 1 | 3.31 ng/mL | Standard Deviation 4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE: Cycle 1 | 676 ng/mL | Standard Deviation 176 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Unconjugated MMAE: Cycle 1 | 2.21 ng/mL | Standard Deviation 1.34 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE: Cycle 1 | 634 ng/mL | Standard Deviation 158 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE: Cycle 2 | 694 ng/mL | Standard Deviation 138 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | acMMAE: Cycle 4 | 759 ng/mL | Standard Deviation 107 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab: Cycle 1 | 37.6 ng/mL | Standard Deviation 9.42 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab: Cycle 2 | 40.6 ng/mL | Standard Deviation 9.46 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a | Total Ab: Cycle 4 | 44.8 ng/mL | Standard Deviation 5.06 |
Secondary
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for bendamustine and rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a | acMMAE | 73.0 mL/kg | Geometric Coefficient of Variation 22.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a | Total Ab | 82.3 mL/kg | Geometric Coefficient of Variation 9.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a | acMMAE | 82.7 mL/kg | Geometric Coefficient of Variation 33.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a | Total Ab | 76.6 mL/kg | Geometric Coefficient of Variation 25.7 |
Secondary
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Cohort 1b (Phase Ib) who received at least one study treatment and who provided suitable PK samples. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for bendamustine and obinutuzumab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE | 77.2 mL/kg | Standard Deviation 38.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab | 87.5 mL/kg | Standard Deviation 38.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | Total Ab | 87.9 mL/kg | Standard Deviation 24.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b | acMMAE | 64.7 mL/kg | Standard Deviation 23 |
Secondary
Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms B and D who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D | Bendamustine | 2.86 h*ug/mL | Geometric Coefficient of Variation 67.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D | Bendamustine | 3.43 h*ug/mL | Geometric Coefficient of Variation 97.4 |
Secondary
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for pola and obinutuzumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F | Bendamustine | 2.88 h*ug/mL | Geometric Coefficient of Variation 28.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F | Bendamustine | 4.10 h*ug/mL | Geometric Coefficient of Variation 67.4 |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F | acMMAE | — h*ug/mL | — |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F | Total Ab | — h*ug/mL | — |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F | Unconjugated MMAE | — h*ug/mL | — |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F | Obinutuzumab | — h*ug/mL | — |
Secondary
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms A and C who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for pola and rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Bendamustine | 3.29 h*ug/mL | Geometric Coefficient of Variation 73.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Bendamustine | 3.62 h*ug/mL | Geometric Coefficient of Variation 78.5 |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | acMMAE | — h*ug/mL | — |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Total Ab | — h*ug/mL | — |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Unconjugated MMAE | — h*ug/mL | — |
| Unknown | Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Rituximab | — h*ug/mL | — |
Secondary
Phase II: CL of Bendamustine and Rituximab in Arms B and D
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms B and D who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: CL of Bendamustine and Rituximab in Arms B and D | Bendamustine | 54.4 L/h | Geometric Coefficient of Variation 60.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: CL of Bendamustine and Rituximab in Arms B and D | Bendamustine | 46.4 L/h | Geometric Coefficient of Variation 93.9 |
Secondary
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema AUC was not evaluated for pola and obinutuzumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Bendamustine | 61.3 L/h | Geometric Coefficient of Variation 33.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Bendamustine | 39.9 L/h | Geometric Coefficient of Variation 76.1 |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | acMMAE | — L/h | — |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Total Ab | — L/h | — |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Uncojugated MMAE | — L/h | — |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Obinutuzumab | — L/h | — |
Secondary
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms A and B who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema CL was not evaluated for pola and rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Bendamustine | 47.9 Liters per hour (L/h) | Geometric Coefficient of Variation 60.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Bendamustine | 42.6 Liters per hour (L/h) | Geometric Coefficient of Variation 66.4 |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | acMMAE | — Liters per hour (L/h) | — |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Total Ab | — Liters per hour (L/h) | — |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Unconjugated MMAE | — Liters per hour (L/h) | — |
| Unknown | Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Rituximab | — Liters per hour (L/h) | — |
Secondary
Phase II: Cmax of Bendamustine and Rituximab in Arms B and D
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms B and D who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Bendamustine and Rituximab in Arms B and D | Bendamustine | 3.21 ug/mL | Standard Deviation 2.09 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Bendamustine and Rituximab in Arms B and D | Rituximab | 207 ug/mL | Standard Deviation 50.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Bendamustine and Rituximab in Arms B and D | Bendamustine | 3.85 ug/mL | Standard Deviation 2.91 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Bendamustine and Rituximab in Arms B and D | Rituximab | 183 ug/mL | Standard Deviation 33.6 |
Secondary
Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody and unconjugated MMAE were measured.
Time frame: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms A and C who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | acMMAE: Cycle 1 | 622 ng/mL | Standard Deviation 194 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | acMMAE: Cycle 4 | 703 ng/mL | Standard Deviation 150 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Total Ab: Cycle 1 | 36.7 ng/mL | Standard Deviation 9.54 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Total Ab: Cycle 4 | 46.1 ng/mL | Standard Deviation 11.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Bendamustine: Cycle 1 | 3.57 ng/mL | Standard Deviation 2.06 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Rituximab: Cycle 1 | 188 ng/mL | Standard Deviation 49.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Bendamustine: Cycle 1 | 4.23 ng/mL | Standard Deviation 2.26 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | acMMAE: Cycle 1 | 661 ng/mL | Standard Deviation 149 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Total Ab: Cycle 4 | 41.4 ng/mL | Standard Deviation 8.29 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | acMMAE: Cycle 4 | 659 ng/mL | Standard Deviation 135 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Rituximab: Cycle 1 | 191 ng/mL | Standard Deviation 35.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C | Total Ab: Cycle 1 | 35.7 ng/mL | Standard Deviation 8.5 |
Secondary
Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F
PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured.
Time frame: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Total Ab: Cycle 1 | 33.3 ug/mL | Standard Deviation 8.04 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Bendamustine: Cycle 1 | 3.30 ug/mL | Standard Deviation 1.58 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | acMMAE: Cycle 4 | 845 ug/mL | Standard Deviation 165 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Obinutuzumab: Cycle 1 | 349 ug/mL | Standard Deviation 72.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Total Ab: Cycle 4 | 56.1 ug/mL | Standard Deviation 11.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Obinutuzumab: Cycle 4 | 727 ug/mL | Standard Deviation 217 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | acMMAE: Cycle 1 | 692 ug/mL | Standard Deviation 230 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Obinutuzumab: Cycle 4 | 666 ug/mL | Standard Deviation 190 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | acMMAE: Cycle 1 | 703 ug/mL | Standard Deviation 211 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | acMMAE: Cycle 4 | 713 ug/mL | Standard Deviation 70.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Total Ab: Cycle 1 | 39.0 ug/mL | Standard Deviation 7.63 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Total Ab: Cycle 4 | 37.8 ug/mL | Standard Deviation 4.51 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Bendamustine: Cycle 1 | 5.47 ug/mL | Standard Deviation 4.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F | Obinutuzumab: Cycle 1 | 274 ug/mL | Standard Deviation 118 |
Secondary
Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II Expansion Cohorts and Arm G (Phase II NF Cohort) irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 65.0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 33.3 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC | 35.7 percentage of participants |
Secondary
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. 'Overall Number Analyzed' are the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator | 11.335 months |
Secondary
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. 'Overall Number Analyzed' are the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC | 13.437 months |
Secondary
Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator
EFS was defined as time from randomization to disease progression or relapse, as assessed by the investigator or death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator | 5.092 months |
Secondary
Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
CR was assessed by Investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 36.8 percentage of participants |
Secondary
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately\>liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator | 42.5 percentage of participants |
Secondary
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 43.4 percentage of participants |
Secondary
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator
PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator | 5.881 months |
Secondary
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC
PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC | 6.965 months |
Secondary
Phase II NF Cohorts: Overall Survival (OS)
OS was defined as the time from the date of randomization or first treatment (for obinutuzumab arms) to the date of death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohorts: Overall Survival (OS) | 12.320 months |
Secondary
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator
BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes & ELS, score=4 or 5, reduced UT than BL & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator | 62.3 percentage of participants |
Secondary
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC
BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes & ELS, score=4 or 5, reduced UT than BL & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Population: ITT population included all randomized participants in Phase II NF Cohort irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC | 57.5 percentage of participants |
Secondary
Phase II: Percentage of Participants With AEs
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Time frame: From the study start up to the end of the study (up to approximately 84 months)
Population: Safety population consisted of all ITT participants from Phase II who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With AEs | 100 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With AEs | 100 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With AEs | 100 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With AEs | 97.4 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With AEs | 100 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With AEs | 100 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With AEs | 99.1 percentage of participants |
Secondary
Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator
BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN & ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver &/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN & ELS, score=4 or 5, reduced UT than baseline (BL) & residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi & no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | 89.7 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | 90.2 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | 70.0 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | 32.5 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | 90.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | 52.4 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator | 62.3 percentage of participants |
p-value: 0.93995% CI: [-15.07, 13.71]Cochran-Mantel-Haenszel
p-value: 0.000695% CI: [15.64, 54.71]Cochran-Mantel-Haenszel
Secondary
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
CR was determined by investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimetres (cm) in in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 46.2 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 19.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 20.0 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 5.0 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 20.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 14.3 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator | 14.2 percentage of participants |
Secondary
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
CR was determined by IRC a at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 41.0 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 36.6 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 22.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 2.5 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 50.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 23.8 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC | 17.9 percentage of participants |
Secondary
Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
CR was assessed by investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 64.1 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 63.4 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 42.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 15.0 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 65.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 33.3 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator | 36.8 percentage of participants |
p-value: 0.881795% CI: [-19.68, 20.86]Cochran-Mantel-Haenszel
p-value: 0.006195% CI: [7.66, 44.74]Cochran-Mantel-Haenszel
Secondary
Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 79.5 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 80.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 47.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 17.5 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 85.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 33.3 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator | 42.5 percentage of participants |
p-value: 0.952395% CI: [-18.66, 16.46]Cochran-Mantel-Haenszel
p-value: 0.003695% CI: [9.48, 47.37]Cochran-Mantel-Haenszel
Secondary
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 79.5 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 75.6 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 45.0 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 15.0 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 80.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 33.3 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator | 42.5 percentage of participants |
p-value: 0.622595% CI: [-14.49, 21.72]Cochran-Mantel-Haenszel
p-value: 0.003295% CI: [9.94, 47.12]Cochran-Mantel-Haenszel
Secondary
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 74.4 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 80.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 40.0 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 15.0 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 80.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 38.1 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC | 41.5 percentage of participants |
p-value: 0.483595% CI: [-24.14, 12.12]Cochran-Mantel-Haenszel
p-value: 0.009695% CI: [5.39, 42.33]Cochran-Mantel-Haenszel
Secondary
Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. Bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Population: ITT population included all randomized participants in Phase II irrespective of whether or not they received the study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 76.9 percentage of participants |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 73.2 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 42.5 percentage of participants |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 17.5 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 85.0 percentage of participants |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 38.1 percentage of participants |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC | 43.4 percentage of participants |
p-value: 0.657495% CI: [-15.14, 22.11]Cochran-Mantel-Haenszel
p-value: 0.012895% CI: [4.89, 42.63]Cochran-Mantel-Haenszel
Secondary
Phase II: Vss of Bendamustine and Rituximab in Arms B and D
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms B and D who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Vss of Bendamustine and Rituximab in Arms B and D | Bendamustine | 44.9 L | Geometric Coefficient of Variation 69.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Vss of Bendamustine and Rituximab in Arms B and D | Bendamustine | 33.2 L | Geometric Coefficient of Variation 62.9 |
Secondary
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms E and F who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for pola and obinutuzumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Bendamustine | 51.2 L | Geometric Coefficient of Variation 33.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Bendamustine | 31.5 L | Geometric Coefficient of Variation 68.1 |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | acMMAE | — L | — |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Total Ab | — L | — |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Unconjugated MMAE | — L | — |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F | Obinutuzumab | — L | — |
Secondary
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Population: PK evaluable population included all the ITT participants in Arms A and C who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoints. Due to the sparse sample collection schema Vss was not evaluated for pola and rituximab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Bendamustine | 36.5 L | Geometric Coefficient of Variation 86.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Bendamustine | 34.3 L | Geometric Coefficient of Variation 57.7 |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | acMMAE | — L | — |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Total Ab | — L | — |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Unconjugated MMAE | — L | — |
| Unknown | Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C | Rituximab | — L | — |
Secondary
Plasma Concentration of Bendamustine
Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H).
Time frame: Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose
Population: PK evaluable population included all the ITT participants Phase Ib and Phase II who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 5 min Post Dose | 2130 ng/mL | Geometric Coefficient of Variation 665.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 1h Post Dose | 456 ng/mL | Geometric Coefficient of Variation 167.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 2h Post Dose | 84.4 ng/mL | Geometric Coefficient of Variation 173.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 3h Post Dose | 20.5 ng/mL | Geometric Coefficient of Variation 220.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 4h Post Dose | 7.60 ng/mL | Geometric Coefficient of Variation 278.5 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 5 min Post Dose | 2810 ng/mL | Geometric Coefficient of Variation 222.7 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 2h Post Dose | 55.1 ng/mL | Geometric Coefficient of Variation 236.5 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 4h Post Dose | 4.58 ng/mL | Geometric Coefficient of Variation 268.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 1h Post Dose | 353 ng/mL | Geometric Coefficient of Variation 187.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 3h Post Dose | 12.7 ng/mL | Geometric Coefficient of Variation 246.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 4h Post Dose | 8.11 ng/mL | Geometric Coefficient of Variation 724.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 3h Post Dose | 23.5 ng/mL | Geometric Coefficient of Variation 461 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 2h Post Dose | 93.8 ng/mL | Geometric Coefficient of Variation 250.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 1h Post Dose | 518 ng/mL | Geometric Coefficient of Variation 154.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 5 min Post Dose | 2740 ng/mL | Geometric Coefficient of Variation 550.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 2h Post Dose | 101 ng/mL | Geometric Coefficient of Variation 375.8 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 5 min Post Dose | 1700 ng/mL | Geometric Coefficient of Variation 1865.5 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 1h Post Dose | 451 ng/mL | Geometric Coefficient of Variation 380.2 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 4h Post Dose | 8.08 ng/mL | Geometric Coefficient of Variation 615.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 3h Post Dose | 21.5 ng/mL | Geometric Coefficient of Variation 509.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm E (Phase II Expansion): Pola+BG in FL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm E (Phase II Expansion): Pola+BG in FL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 3h Post Dose | 12.4 ng/mL | Geometric Coefficient of Variation 132 |
| Arm E (Phase II Expansion): Pola+BG in FL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 5 min Post Dose | 3090 ng/mL | Geometric Coefficient of Variation 68.3 |
| Arm E (Phase II Expansion): Pola+BG in FL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 1h Post Dose | 478 ng/mL | Geometric Coefficient of Variation 111.4 |
| Arm E (Phase II Expansion): Pola+BG in FL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 2h Post Dose | 62.8 ng/mL | Geometric Coefficient of Variation 104.3 |
| Arm E (Phase II Expansion): Pola+BG in FL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 4h Post Dose | 3.30 ng/mL | Geometric Coefficient of Variation 147.2 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 2h Post Dose | 128 ng/mL | Geometric Coefficient of Variation 196.7 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 1h Post Dose | 639 ng/mL | Geometric Coefficient of Variation 165.6 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 3h Post Dose | 28.2 ng/mL | Geometric Coefficient of Variation 287.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 4h Post Dose | 6.18 ng/mL | Geometric Coefficient of Variation 131 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: 5 min Post Dose | 3790 ng/mL | Geometric Coefficient of Variation 119.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Bendamustine | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
Secondary
Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Time frame: Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Population: PK evaluable population included all the ITT participants in Phase Ib and Phase II who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: 30 min Post Dose | 685 ng/mL | Geometric Coefficient of Variation 22 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 12.2 ng/mL | Geometric Coefficient of Variation 26.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 654 ng/mL | Geometric Coefficient of Variation 29.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 748 ng/mL | Geometric Coefficient of Variation 23.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 8 | 29.4 ng/mL | Geometric Coefficient of Variation 5887.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 15 | 12.2 ng/mL | Geometric Coefficient of Variation 1626.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 3.21 ng/mL | Geometric Coefficient of Variation 546.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 12.4 ng/mL | Geometric Coefficient of Variation 47.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 754 ng/mL | Geometric Coefficient of Variation 14.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 8 | 75.9 ng/mL | Geometric Coefficient of Variation 40.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 617 ng/mL | Geometric Coefficient of Variation 26.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 21.1 ng/mL | Geometric Coefficient of Variation 46.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 15 | 25.4 ng/mL | Geometric Coefficient of Variation 29.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: 30 min Post Dose | 683 ng/mL | Geometric Coefficient of Variation 20.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 15.3 ng/mL | Geometric Coefficient of Variation 61.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 15 | 28.9 ng/mL | Geometric Coefficient of Variation 48.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: 30 min Post Dose | 803 ng/mL | Geometric Coefficient of Variation 20.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 734 ng/mL | Geometric Coefficient of Variation 22 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 8.75 ng/mL | Geometric Coefficient of Variation 77.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 8 | 90.7 ng/mL | Geometric Coefficient of Variation 46.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Study Treatment Completion | 18.7 ng/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 719 ng/mL | Geometric Coefficient of Variation 26.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 716 ng/mL | Geometric Coefficient of Variation 13.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 718 ng/mL | Geometric Coefficient of Variation 14.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 26.2 ng/mL | Geometric Coefficient of Variation 22.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 8 | 109 ng/mL | Geometric Coefficient of Variation 48.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 15 | 34.4 ng/mL | Geometric Coefficient of Variation 37.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: 30 min Post Dose | 834 ng/mL | Geometric Coefficient of Variation 13.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 16.6 ng/mL | Geometric Coefficient of Variation 25.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Unscheduled Visit: Pre-dose | 1.21 ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 492 ng/mL | Geometric Coefficient of Variation 241.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 4.72 ng/mL | Geometric Coefficient of Variation 159.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 11.2 ng/mL | Geometric Coefficient of Variation 109.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 689 ng/mL | Geometric Coefficient of Variation 20.9 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Study Treatment Completion | 10.7 ng/mL | Geometric Coefficient of Variation 181.7 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Study Treatment Completion | 14.2 ng/mL | Geometric Coefficient of Variation 95.7 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 20.7 ng/mL | Geometric Coefficient of Variation 46.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 643 ng/mL | Geometric Coefficient of Variation 24.7 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 645 ng/mL | Geometric Coefficient of Variation 21.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Unscheduled Visit | 41.1 ng/mL | Geometric Coefficient of Variation 49.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Unscheduled Visit: Pre-dose | 0.180 ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Unscheduled Visit: 30 min Post Dose | 915 ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 12.7 ng/mL | Geometric Coefficient of Variation 120.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Study Treatment Completion | 14.9 ng/mL | Geometric Coefficient of Variation 69.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 829 ng/mL | Geometric Coefficient of Variation 20.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 9.05 ng/mL | Geometric Coefficient of Variation 74.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Unscheduled Visit | 53.0 ng/mL | Geometric Coefficient of Variation 58 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 15.2 ng/mL | Geometric Coefficient of Variation 30.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 453 ng/mL | Geometric Coefficient of Variation 682.8 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: Pre-dose | 19.6 ng/mL | Geometric Coefficient of Variation 30.5 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 4 Day 1: 30 min Post Dose | 709 ng/mL | Geometric Coefficient of Variation 10.1 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: 30 min Post Dose | 472 ng/mL | Geometric Coefficient of Variation 617.2 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 2 Day 1: Pre-dose | 13.1 ng/mL | Geometric Coefficient of Variation 45.2 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Study Treatment Completion | 12.3 ng/mL | Geometric Coefficient of Variation 109.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
Secondary
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Time frame: Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Population: PK evaluable population included all the ITT participants Phase Ib and Phase II who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: 30 min Post Dose | 0.185 ng/mL | Geometric Coefficient of Variation 54.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.726 ng/mL | Geometric Coefficient of Variation 297.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.234 ng/mL | Geometric Coefficient of Variation 35 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 8 | 1.48 ng/mL | Geometric Coefficient of Variation 100.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 15 | 0.311 ng/mL | Geometric Coefficient of Variation 93.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0264 ng/mL | Geometric Coefficient of Variation 70.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.0414 ng/mL | Geometric Coefficient of Variation 102.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.133 ng/mL | Geometric Coefficient of Variation 72.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: 30 min Post Dose | 0.263 ng/mL | Geometric Coefficient of Variation 72.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.266 ng/mL | Geometric Coefficient of Variation 27 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.234 ng/mL | Geometric Coefficient of Variation 80.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.158 ng/mL | Geometric Coefficient of Variation 79.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 8 | 1.84 ng/mL | Geometric Coefficient of Variation 78.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 15 | 0.531 ng/mL | Geometric Coefficient of Variation 88.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.397 ng/mL | Geometric Coefficient of Variation 67.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 15 | 0.705 ng/mL | Geometric Coefficient of Variation 60 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: 30 min Post Dose | 0.231 ng/mL | Geometric Coefficient of Variation 53.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 8 | 1.96 ng/mL | Geometric Coefficient of Variation 51.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0512 ng/mL | Geometric Coefficient of Variation 129.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.0511 ng/mL | Geometric Coefficient of Variation 68.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Treatment Completion | 0.0595 ng/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.167 ng/mL | Geometric Coefficient of Variation 39.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.257 ng/mL | Geometric Coefficient of Variation 32.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.327 ng/mL | Geometric Coefficient of Variation 41.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.150 ng/mL | Geometric Coefficient of Variation 44.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.150 ng/mL | Geometric Coefficient of Variation 44.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 8 | 2.34 ng/mL | Geometric Coefficient of Variation 21.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 15 | 0.688 ng/mL | Geometric Coefficient of Variation 19.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: 30 min Post Dose | 0.345 ng/mL | Geometric Coefficient of Variation 31.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Unscheduled Visit: Pre-dose | 0.0180 ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.402 ng/mL | Geometric Coefficient of Variation 80.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0373 ng/mL | Geometric Coefficient of Variation 81.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.0554 ng/mL | Geometric Coefficient of Variation 77.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.198 ng/mL | Geometric Coefficient of Variation 32 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Treatment Completion | 0.0506 ng/mL | Geometric Coefficient of Variation 113 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.159 ng/mL | Geometric Coefficient of Variation 80.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.316 ng/mL | Geometric Coefficient of Variation 38.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Unscheduled Visit: 30 min Post Dose | 0.114 ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Unscheduled Visit: Pre-dose | 0.0180 ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Treatment Completion | 0.0749 ng/mL | Geometric Coefficient of Variation 165.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.315 ng/mL | Geometric Coefficient of Variation 105.3 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.158 ng/mL | Geometric Coefficient of Variation 58.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.195 ng/mL | Geometric Coefficient of Variation 38.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.243 ng/mL | Geometric Coefficient of Variation 101.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Treatment Completion | 0.0682 ng/mL | Geometric Coefficient of Variation 110.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Unscheduled Visit | 0.738 ng/mL | Geometric Coefficient of Variation 64.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.0481 ng/mL | Geometric Coefficient of Variation 83.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.0451 ng/mL | Geometric Coefficient of Variation 76.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: 30 min Post Dose | 0.456 ng/mL | Geometric Coefficient of Variation 103.1 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Treatment Completion | 0.150 ng/mL | Geometric Coefficient of Variation 179.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 2 Day 1: Pre-dose | 0.186 ng/mL | Geometric Coefficient of Variation 86.8 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: Pre-dose | 0.141 ng/mL | Geometric Coefficient of Variation 102.3 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Cycle 4 Day 1: 30 min Post Dose | 0.283 ng/mL | Geometric Coefficient of Variation 56.9 |
Secondary
Serum Concentration of Obinutuzumab
Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Time frame: Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Population: PK evaluable population included all the ITT participants who Cohort 1b (Phase 1b) and Arms E and F (Phase II) received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Follow up on Month 6, Day 1 | 11.5 g/mL | Geometric Coefficient of Variation 56.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Cycle 4 Day 1: Pre-dose | 293 g/mL | Geometric Coefficient of Variation 53.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Follow up on Month 24, Day 1 | 0.00203 g/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Follow up on Month 3, Day 1 | 67.7 g/mL | Geometric Coefficient of Variation 47.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Follow up on Month 18, Day 1 | 0.00978 g/mL | Geometric Coefficient of Variation 1188.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Follow up on Month 12, Day 1 | 0.237 g/mL | Geometric Coefficient of Variation 717.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Cycle 2 Day 1: Pre-dose | 283 g/mL | Geometric Coefficient of Variation 38.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Study Treatment Completion Visit | 367 g/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of Obinutuzumab | Cycle 1 Day 1: Pre-dose | NA g/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 6, Day 1 | 5.38 g/mL | Geometric Coefficient of Variation 12.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Cycle 1 Day 1: Pre-dose | NA g/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Cycle 2 Day 1: Pre-dose | 412 g/mL | Geometric Coefficient of Variation 40.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Cycle 4 Day 1: Pre-dose | 359 g/mL | Geometric Coefficient of Variation 28.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 3, Day 1 | 28.8 g/mL | Geometric Coefficient of Variation 17 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 12, Day 1 | 0.389 g/mL | Geometric Coefficient of Variation 119.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 18, Day 1 | 0.0107 g/mL | Geometric Coefficient of Variation 170.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 24, Day 1 | 0.00203 g/mL | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of Obinutuzumab | Unscheduled | 3.09 g/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Follow up on Month 3, Day 1 | 38.5 g/mL | Geometric Coefficient of Variation 167.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Cycle 2 Day 1: Pre-dose | 301 g/mL | Geometric Coefficient of Variation 39.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Follow up on Month 6, Day 1 | 7.64 g/mL | Geometric Coefficient of Variation 412.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Follow up on Month 12, Day 1 | 0.162 g/mL | Geometric Coefficient of Variation 569.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Cycle 1 Day 1: 30 min Post Dose | 341 g/mL | Geometric Coefficient of Variation 22.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Cycle 1 Day 1: Pre-dose | NA g/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Follow up on Month 18, Day 1 | 0.00842 g/mL | Geometric Coefficient of Variation 347.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Study Treatment Completion Visit | 242 g/mL | Geometric Coefficient of Variation 52.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Unscheduled | 20.8 g/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Cycle 4 Day 1: 30 min Post Dose | 701 g/mL | Geometric Coefficient of Variation 27.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Obinutuzumab | Cycle 4 Day 1: Pre-dose | 291 g/mL | Geometric Coefficient of Variation 37.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Cycle 4 Day 1: 30 min Post Dose | 642 g/mL | Geometric Coefficient of Variation 29.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Cycle 4 Day 1: Pre-dose | 290 g/mL | Geometric Coefficient of Variation 36.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 18, Day 1 | 0.0460 g/mL | Geometric Coefficient of Variation 86.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 3, Day 1 | 55.1 g/mL | Geometric Coefficient of Variation 119.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Cycle 2 Day 1: Pre-dose | 349 g/mL | Geometric Coefficient of Variation 58 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Cycle 1 Day 1: Pre-dose | NA g/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Unscheduled Visit: Pre-dose | 0.0626 g/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 6, Day 1 | 15.8 g/mL | Geometric Coefficient of Variation 137.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Cycle 1 Day 1: 30 min Post Dose | 221 g/mL | Geometric Coefficient of Variation 105.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Unscheduled Visit: 30 min Post Dose | 349 g/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 24, Day 1 | 0.00203 g/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Follow up on Month 12, Day 1 | 0.732 g/mL | Geometric Coefficient of Variation 18.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Obinutuzumab | Study Treatment Completion Visit | 232 g/mL | Geometric Coefficient of Variation 46.2 |
Secondary
Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab
PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Time frame: Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)
Population: PK evaluable population included all the ITT participants Phase Ib and Phase II who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 15 | 1.83 grams per milliliters (g/mL) | Geometric Coefficient of Variation 1784.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 40.2 grams per milliliters (g/mL) | Geometric Coefficient of Variation 27.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 18, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 8 | 3.43 grams per milliliters (g/mL) | Geometric Coefficient of Variation 4393.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 3.44 grams per milliliters (g/mL) | Geometric Coefficient of Variation 30.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: 30 min Post Dose | 35.8 grams per milliliters (g/mL) | Geometric Coefficient of Variation 25.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 24, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 33.2 grams per milliliters (g/mL) | Geometric Coefficient of Variation 28.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.164 grams per milliliters (g/mL) | Geometric Coefficient of Variation 51.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 0.696 grams per milliliters (g/mL) | Geometric Coefficient of Variation 941.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.771 grams per milliliters (g/mL) | Geometric Coefficient of Variation 193.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 44.6 grams per milliliters (g/mL) | Geometric Coefficient of Variation 11 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 24, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 36.6 grams per milliliters (g/mL) | Geometric Coefficient of Variation 25.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 18, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 8 | 9.01 grams per milliliters (g/mL) | Geometric Coefficient of Variation 43.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 15 | 4.26 grams per milliliters (g/mL) | Geometric Coefficient of Variation 35.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 2.31 grams per milliliters (g/mL) | Geometric Coefficient of Variation 54.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.0788 grams per milliliters (g/mL) | Geometric Coefficient of Variation 230 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: 30 min Post Dose | 39.5 grams per milliliters (g/mL) | Geometric Coefficient of Variation 28.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 5.03 grams per milliliters (g/mL) | Geometric Coefficient of Variation 59 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: 30 min Post Dose | 43.4 grams per milliliters (g/mL) | Geometric Coefficient of Variation 31.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 2.20 grams per milliliters (g/mL) | Geometric Coefficient of Variation 76.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Study Treatment Completion Visit | 5.34 grams per milliliters (g/mL) | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 24, Day 1 | 0.0250 grams per milliliters (g/mL) | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.219 grams per milliliters (g/mL) | Geometric Coefficient of Variation 96.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.910 grams per milliliters (g/mL) | Geometric Coefficient of Variation 82.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 8 | 10.2 grams per milliliters (g/mL) | Geometric Coefficient of Variation 39.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0298 grams per milliliters (g/mL) | Geometric Coefficient of Variation 35.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 18, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 43.0 grams per milliliters (g/mL) | Geometric Coefficient of Variation 25.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 15 | 4.61 grams per milliliters (g/mL) | Geometric Coefficient of Variation 40.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 4.61 grams per milliliters (g/mL) | Geometric Coefficient of Variation 62.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 37.5 grams per milliliters (g/mL) | Geometric Coefficient of Variation 29.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 47.1 grams per milliliters (g/mL) | Geometric Coefficient of Variation 24.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 34.3 grams per milliliters (g/mL) | Geometric Coefficient of Variation 20.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 8 | 10.0 grams per milliliters (g/mL) | Geometric Coefficient of Variation 31.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 15 | 5.22 grams per milliliters (g/mL) | Geometric Coefficient of Variation 28.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 3.70 grams per milliliters (g/mL) | Geometric Coefficient of Variation 27.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: 30 min Post Dose | 42.2 grams per milliliters (g/mL) | Geometric Coefficient of Variation 22.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 6.26 grams per milliliters (g/mL) | Geometric Coefficient of Variation 18.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.394 grams per milliliters (g/mL) | Geometric Coefficient of Variation 27.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.104 grams per milliliters (g/mL) | Geometric Coefficient of Variation 18.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 18, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 24, Day 1 | 0.0250 grams per milliliters (g/mL) | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit | 0.0250 grams per milliliters (g/mL) | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 35.4 grams per milliliters (g/mL) | Geometric Coefficient of Variation 27.7 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit: Pre-dose | 0.279 grams per milliliters (g/mL) | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 1.23 grams per milliliters (g/mL) | Geometric Coefficient of Variation 203.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Study Treatment Completion Visit | 3.34 grams per milliliters (g/mL) | Geometric Coefficient of Variation 180.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 3.61 grams per milliliters (g/mL) | Geometric Coefficient of Variation 97.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 18, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.265 grams per milliliters (g/mL) | Geometric Coefficient of Variation 209.9 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.0539 grams per milliliters (g/mL) | Geometric Coefficient of Variation 145.7 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 44.8 grams per milliliters (g/mL) | Geometric Coefficient of Variation 24.3 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 5.72 grams per milliliters (g/mL) | Geometric Coefficient of Variation 39.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.316 grams per milliliters (g/mL) | Geometric Coefficient of Variation 266.2 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 40.6 grams per milliliters (g/mL) | Geometric Coefficient of Variation 20.6 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.0564 grams per milliliters (g/mL) | Geometric Coefficient of Variation 195.7 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 2.48 grams per milliliters (g/mL) | Geometric Coefficient of Variation 137.6 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0301 grams per milliliters (g/mL) | Geometric Coefficient of Variation 60.6 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 34.6 grams per milliliters (g/mL) | Geometric Coefficient of Variation 26.2 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Study Treatment Completion Visit | 4.33 grams per milliliters (g/mL) | Geometric Coefficient of Variation 69.4 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit | 1.65 grams per milliliters (g/mL) | Geometric Coefficient of Variation 5419.8 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit: Pre-dose | 0.0250 grams per milliliters (g/mL) | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit: 30 min Post Dose | 42.0 grams per milliliters (g/mL) | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.0920 grams per milliliters (g/mL) | Geometric Coefficient of Variation 123.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 55.0 grams per milliliters (g/mL) | Geometric Coefficient of Variation 21.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 2.20 grams per milliliters (g/mL) | Geometric Coefficient of Variation 100.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 18, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Study Treatment Completion Visit | 4.57 grams per milliliters (g/mL) | Geometric Coefficient of Variation 57.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Unscheduled Visit | 1.23 grams per milliliters (g/mL) | Geometric Coefficient of Variation 30267.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 4.82 grams per milliliters (g/mL) | Geometric Coefficient of Variation 20.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 32.4 grams per milliliters (g/mL) | Geometric Coefficient of Variation 22.8 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.489 grams per milliliters (g/mL) | Geometric Coefficient of Variation 174.2 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Study Treatment Completion Visit | 3.23 grams per milliliters (g/mL) | Geometric Coefficient of Variation 79.3 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: Pre-dose | 5.03 grams per milliliters (g/mL) | Geometric Coefficient of Variation 29.3 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 12, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 3, Day 1 | 0.543 grams per milliliters (g/mL) | Geometric Coefficient of Variation 126.7 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 18, Day 1 | 0.0250 grams per milliliters (g/mL) | Geometric Coefficient of Variation 0 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: Pre-dose | NA grams per milliliters (g/mL) | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 1 Day 2: 30 min Post Dose | 38.3 grams per milliliters (g/mL) | Geometric Coefficient of Variation 20.3 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 4 Day 1: 30 min Post Dose | 37.5 grams per milliliters (g/mL) | Geometric Coefficient of Variation 11.6 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 6, Day 1 | 0.150 grams per milliliters (g/mL) | Geometric Coefficient of Variation 206.6 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Follow up on Month 24, Day 1 | 0.0250 grams per milliliters (g/mL) | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab | Cycle 2 Day 1: Pre-dose | 2.83 grams per milliliters (g/mL) | Geometric Coefficient of Variation 41.8 |
Secondary
Serum Concentration of Rituximab
Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H).
Time frame: Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)
Population: PK evaluable population included all the ITT participants in Cohort 1a (Phase Ib) and Arms A-D (Phase II) who received at least one study treatment and who provided suitable PK samples. 'Overall Number Analyzed' are the number of participants with data available for analysis. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Rituximab | Cycle 1 Days 1: Pre-dose | NA ng/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Rituximab | Cycle 2 Days 1: Pre-dose | 22.8 ng/mL | Geometric Coefficient of Variation 79.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Rituximab | Unscheduled: Pre-dose | 30.6 ng/mL | Geometric Coefficient of Variation 118 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Rituximab | Cycle 1 Days 1: 30 min Post Dose | 182 ng/mL | Geometric Coefficient of Variation 27.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Serum Concentration of Rituximab | Cycle 4 Days 1: Pre-dose | 65.1 ng/mL | Geometric Coefficient of Variation 46.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 4 Days 1: Pre-dose | 62.3 ng/mL | Geometric Coefficient of Variation 42.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 2 Days 1: Pre-dose | 20.2 ng/mL | Geometric Coefficient of Variation 145.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 1 Days 1: Pre-dose | NA ng/mL | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 1 Days 1: 30 min Post Dose | 202 ng/mL | Geometric Coefficient of Variation 24.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of Rituximab | Unscheduled: Pre-dose | 298 ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of Rituximab | Cycle 1 Days 1: Pre-dose | NA ng/mL | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of Rituximab | Cycle 1 Days 1: 30 min Post Dose | 188 ng/mL | Geometric Coefficient of Variation 19.9 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of Rituximab | Cycle 2 Days 1: Pre-dose | 34.9 ng/mL | Geometric Coefficient of Variation 89.9 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Serum Concentration of Rituximab | Cycle 4 Days 1: Pre-dose | 74.7 ng/mL | Geometric Coefficient of Variation 50.9 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 1 Days 1: 30 min Post Dose | 180 ng/mL | Geometric Coefficient of Variation 18 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 1 Days 1: Pre-dose | NA ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of Rituximab | Unscheduled: Pre-dose | 2.00 ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 4 Days 1: Pre-dose | 83.3 ng/mL | Geometric Coefficient of Variation 49.1 |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of Rituximab | Unscheduled: 30 min Post Dose | 165 ng/mL | — |
| Arm F (Phase II Expansion): Pola+BG in DLBCL | Serum Concentration of Rituximab | Cycle 2 Days 1: Pre-dose | 34.6 ng/mL | Geometric Coefficient of Variation 69.7 |
Secondary
Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F
The TINAS is an 11-item questionnaire that assesses the severity of neuropathy-related symptoms in the last 24 hours. The 11 items assessed were: hot/burning sensations in hands/feet, sensations pins and needles arms/legs, numbness or tingling in hands/feet, sensations of electric shock, pain when touching cold things, cramps in hands/feet, discomfort when touching things, discomfort skin contact with something, trouble grasping small objects, trouble walking loss feeling legs/feet, difficulty balance loss feeling leg/feet. Each item was scored on a 0-10 scale, with 0 being the symptom is not present, and 10 being the symptom is as bad as the participant can imagine. Higher scores indicate more severe disease. Scores were averaged at each week.
Time frame: Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)
Population: ITT population included all randomized participants in Arms A-F (Phase II) irrespective of whether or not they received the study treatment. 'Overall Number Analysed' =number of participants with data available for analysis. 'Number of Participants Analyzed'=number of participants evaluable for this outcome measure. Participants from Arm F did not answer a sufficient number of questions at both baseline and end of treatment visit therefore the average score could not be calculated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 32 | 0.4 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 31 | 0.3 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 30 | 0.7 Points on scale | Standard Deviation 1.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 17 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | End of Treatment | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 29 | 0.2 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 28 | 0.5 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 27 | 0.3 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 18 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 71 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 26 | 0.6 Points on scale | Standard Deviation 0.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 25 | 0.2 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 24 | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 19 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 70 | 0.7 Points on scale | Standard Deviation 1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 23 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 22 | 0.2 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 21 | 0.3 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 20 | 0.0 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 69 | 0.2 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 10 | 0.5 Points on scale | Standard Deviation 0.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 86 | 0.6 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 67 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 66 | 0.6 Points on scale | Standard Deviation 0.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 65 | 0.2 Points on scale | Standard Deviation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 11 | 0.5 Points on scale | Standard Deviation 1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 7 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 64 | 0.4 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 63 | 0.4 Points on scale | Standard Deviation 0.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 62 | 0.7 Points on scale | Standard Deviation 1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 12 | 0.5 Points on scale | Standard Deviation 1.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 84 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 61 | 0.4 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 60 | 0.4 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 59 | 0.0 Points on scale | Standard Deviation 0.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 13 | 0.7 Points on scale | Standard Deviation 1.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 80 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 58 | 0.7 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 57 | 0.3 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 56 | 0.6 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 14 | 0.6 Points on scale | Standard Deviation 1.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Baseline | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 78 | 0.7 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 55 | 0.3 Points on scale | Standard Deviation 0.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 54 | 0.8 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 53 | 0.2 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 1 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 6 | 0.2 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 52 | 0.4 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 2 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 8 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 51 | 0.1 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 50 | 1.0 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 49 | 0.6 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 3 | 0.2 Points on scale | Standard Deviation 0.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 90 | 0.7 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 47 | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 46 | 1.1 Points on scale | Standard Deviation 0.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 45 | 0.8 Points on scale | Standard Deviation 0.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 4 | 0.1 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 75 | 0.2 Points on scale | Standard Deviation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 44 | 1.6 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 43 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 42 | 0.5 Points on scale | Standard Deviation 0.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 5 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 74 | 1.3 Points on scale | Standard Deviation 0.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 41 | 0.6 Points on scale | Standard Deviation 0.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 40 | 0.5 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 39 | 0.7 Points on scale | Standard Deviation 0.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 38 | 0.4 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 37 | 0.4 Points on scale | Standard Deviation 0.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 36 | 0.5 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 15 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 73 | 0.4 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 35 | 0.3 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 34 | 0.2 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 33 | 0.3 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 16 | 0.4 Points on scale | Standard Deviation 0.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 9 | 0.4 Points on scale | Standard Deviation 0.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 14 | 0.7 Points on scale | Standard Deviation 1.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 6 | 0.8 Points on scale | Standard Deviation 1.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 7 | 0.9 Points on scale | Standard Deviation 1.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 8 | 0.8 Points on scale | Standard Deviation 1.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 9 | 0.5 Points on scale | Standard Deviation 0.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 10 | 0.4 Points on scale | Standard Deviation 0.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 11 | 0.5 Points on scale | Standard Deviation 0.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 12 | 0.9 Points on scale | Standard Deviation 2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 13 | 0.6 Points on scale | Standard Deviation 1.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Baseline | 0.5 Points on scale | Standard Deviation 1.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 2 | 0.5 Points on scale | Standard Deviation 1.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 3 | 0.7 Points on scale | Standard Deviation 1.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 4 | 0.8 Points on scale | Standard Deviation 1.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 5 | 0.6 Points on scale | Standard Deviation 1.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 15 | 0.7 Points on scale | Standard Deviation 1.7 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 16 | 0.8 Points on scale | Standard Deviation 1.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 17 | 0.8 Points on scale | Standard Deviation 1.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 18 | 0.7 Points on scale | Standard Deviation 1.8 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 19 | 0.8 Points on scale | Standard Deviation 2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 20 | 0.8 Points on scale | Standard Deviation 1.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 21 | 0.9 Points on scale | Standard Deviation 1.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 22 | 0.8 Points on scale | Standard Deviation 2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 23 | 0.8 Points on scale | Standard Deviation 2.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 24 | 1.0 Points on scale | Standard Deviation 2.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 25 | 0.2 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 26 | 3.3 Points on scale | Standard Deviation 4.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 27 | 1.1 Points on scale | Standard Deviation 2.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 28 | 1.2 Points on scale | Standard Deviation 2.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 29 | 0.8 Points on scale | Standard Deviation 2.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 30 | 0.7 Points on scale | Standard Deviation 1.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 31 | 0.0 Points on scale | Standard Deviation 0.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 32 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 33 | 0.1 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 34 | 1.3 Points on scale | Standard Deviation 2.4 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 35 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 36 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 37 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 38 | 0.1 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 39 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 40 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 41 | 0.7 Points on scale | Standard Deviation 1.6 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 42 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 43 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 44 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 45 | 0.1 Points on scale | Standard Deviation 0.2 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 46 | 0.1 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 47 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 48 | 0.8 Points on scale | Standard Deviation 0.9 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 49 | 0.0 Points on scale | Standard Deviation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 50 | 0.1 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 51 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 52 | 0.4 Points on scale | Standard Deviation 0.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 53 | 0.7 Points on scale | Standard Deviation 1.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 54 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 55 | 0.2 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 56 | 0.2 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 57 | 0.0 Points on scale | Standard Deviation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 59 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 61 | 0.3 Points on scale | Standard Deviation 0.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 63 | 0.0 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 64 | 1.1 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 65 | 0.0 Points on scale | Standard Deviation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 69 | 0.3 Points on scale | Standard Deviation 0.5 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 72 | 1.2 Points on scale | — |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 73 | 0.0 Points on scale | Standard Deviation 0 |
| Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | End of Treatment | 0.6 Points on scale | Standard Deviation 1.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 12 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 60 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 53 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 59 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 26 | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 103 | 0.3 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 54 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 105 | 0.1 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Baseline | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 58 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 55 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 13 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 57 | 1.5 Points on scale | Standard Deviation 2.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 104 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 56 | 0.0 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 84 | 0.6 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 29 | 0.7 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 33 | 1.0 Points on scale | Standard Deviation 1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 18 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 17 | 0.5 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 25 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 34 | 0.8 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 7 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 15 | 0.4 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 24 | 0.5 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 35 | 1.2 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 86 | 0.6 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 23 | 0.6 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 83 | 0.6 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 19 | 0.4 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 36 | 1.2 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 22 | 0.9 Points on scale | Standard Deviation 1.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 28 | 0.5 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 82 | 0.6 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 37 | 1.1 Points on scale | Standard Deviation 0.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 21 | 0.5 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 14 | 0.3 Points on scale | Standard Deviation 0.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 94 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 38 | 1.5 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 81 | 0.6 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 20 | 0.6 Points on scale | Standard Deviation 0.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 80 | 1.1 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 39 | 1.5 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 31 | 1.3 Points on scale | Standard Deviation 0.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 79 | 1.4 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 30 | 0.8 Points on scale | Standard Deviation 0.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 95 | 0.5 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 40 | 0.9 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 78 | 1.4 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 5 | 0.3 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 77 | 1.5 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 41 | 1.4 Points on scale | Standard Deviation 1.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 76 | 0.7 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 75 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 96 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 42 | 0.3 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 8 | 0.2 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 27 | 0.5 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 74 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 43 | 0.6 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 16 | 0.4 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 73 | 1.3 Points on scale | Standard Deviation 1.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 4 | 0.3 Points on scale | Standard Deviation 0.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 72 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 44 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | End of Treatment | 0.5 Points on scale | Standard Deviation 0.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 71 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 98 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 45 | 1.0 Points on scale | Standard Deviation 1.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 9 | 0.2 Points on scale | Standard Deviation 0.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 85 | 0.6 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 70 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 46 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 69 | 1.5 Points on scale | Standard Deviation 2.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 3 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 99 | 0.1 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 47 | 0.1 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 68 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 67 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 48 | 0.2 Points on scale | Standard Deviation 0.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 10 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 66 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 100 | 0.3 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 49 | 1.1 Points on scale | Standard Deviation 1.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 65 | 0.8 Points on scale | Standard Deviation 1.3 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 32 | 1.0 Points on scale | Standard Deviation 0.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 6 | 0.3 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 50 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 64 | 0.1 Points on scale | Standard Deviation 0.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 2 | 0.3 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 11 | 0.2 Points on scale | Standard Deviation 0.2 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 51 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 63 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 62 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 102 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 52 | 0.2 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 61 | 1.5 Points on scale | Standard Deviation 2.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 29 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 30 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 16 | 0.4 Points on scale | Standard Deviation 0.5 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 31 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 6 | 0.7 Points on scale | Standard Deviation 1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 15 | 0.4 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 35 | 0.6 Points on scale | Standard Deviation 0.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 14 | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 39 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 5 | 0.6 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 4 | 0.7 Points on scale | Standard Deviation 0.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 43 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 3 | 0.9 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 2 | 1.0 Points on scale | Standard Deviation 1.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Baseline | 0.6 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 13 | 0.2 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 12 | 0.3 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 11 | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 10 | 0.2 Points on scale | Standard Deviation 0.4 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 9 | 0.5 Points on scale | Standard Deviation 0.7 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | End of Treatment | 0.8 Points on scale | Standard Deviation 1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 8 | 0.6 Points on scale | Standard Deviation 0.9 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 7 | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 20 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 21 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 19 | 0.5 Points on scale | Standard Deviation 0.8 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 22 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 23 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 24 | 0.0 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 18 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 25 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 26 | 0.0 Points on scale | — |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 27 | 0.1 Points on scale | Standard Deviation 0.1 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 17 | 0.4 Points on scale | Standard Deviation 0.6 |
| Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 28 | 0.0 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 33 | 0.2 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 107 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 51 | 0.5 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 63 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 101 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 108 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 50 | 0.5 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 64 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 10 | 0.1 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 100 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 49 | 0.3 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 65 | 0.0 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 15 | 0.9 Points on scale | Standard Deviation 1.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 2 | 0.2 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 66 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 48 | 0.6 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 99 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 67 | 0.9 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 47 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 68 | 1.2 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 9 | 0.1 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | End of Treatment | 0.1 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 46 | 0.5 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 69 | 0.0 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 32 | 0.2 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 98 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 70 | 1.0 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 45 | 0.3 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 3 | 0.0 Points on scale | Standard Deviation 0.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 71 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 44 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 97 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 72 | 0.9 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 8 | 0.2 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 30 | 0.1 Points on scale | Standard Deviation 0.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 43 | 0.4 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 73 | 0.0 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 17 | 0.3 Points on scale | Standard Deviation 0.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 96 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 74 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 42 | 0.5 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 4 | 0.2 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 75 | 1.1 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 41 | 0.3 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 76 | 0.6 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 95 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 77 | 0.9 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 7 | 0.0 Points on scale | Standard Deviation 0.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 40 | 0.1 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 39 | 0.3 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 79 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 89 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 94 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 80 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 5 | 0.1 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 31 | 0.1 Points on scale | Standard Deviation 0.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 20 | 0.3 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 19 | 0.3 Points on scale | Standard Deviation 0.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 38 | 0.3 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 37 | 0.2 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 6 | 0.1 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 21 | 0.3 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 27 | 0.4 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 93 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 36 | 0.1 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 16 | 0.3 Points on scale | Standard Deviation 0.7 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 22 | 0.5 Points on scale | Standard Deviation 0.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 92 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 14 | 0.2 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 35 | 0.4 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 85 | 0.6 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 23 | 0.5 Points on scale | Standard Deviation 0.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 18 | 0.3 Points on scale | Standard Deviation 0.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 83 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 91 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 86 | 0.6 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 24 | 0.3 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 29 | 0.1 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 34 | 0.2 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 90 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 28 | 0.1 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 104 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 13 | 0.3 Points on scale | Standard Deviation 0.4 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 57 | 0.2 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 55 | 0.5 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 103 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 58 | 0.6 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 12 | 0.2 Points on scale | Standard Deviation 0.2 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 54 | 0.5 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 53 | 0.2 Points on scale | Standard Deviation 0.3 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 59 | 0.6 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 25 | 0.1 Points on scale | Standard Deviation 0.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 102 | 0.7 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Baseline | 0.8 Points on scale | Standard Deviation 1.6 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 105 | 0.8 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 52 | 0.5 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 61 | 0.3 Points on scale | Standard Deviation 0.5 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 11 | 0.1 Points on scale | Standard Deviation 0.1 |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 1 | 0.0 Points on scale | — |
| Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL | Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F | Week 62 | 0.6 Points on scale | — |