Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Conditions
Brief summary
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL), followed by post-induction treatment with obinutuzumab in combination with lenalidomide in participants with FL who achieve a complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.
Interventions
DRUGLenalidomide
All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.
DRUGObinutuzumab
Participants will receive a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by post-induction treatment at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months until disease progression or unacceptable toxicity.
DRUGPolatuzumab Vedotin
Participants with R/R FL will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 months during induction treatment. Participants wit R/R DLBCL will receive polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 months during induction treatment.
DRUGRituximab
Participants will receive a fixed dose of rituximab, 375 mg/m\^2 via intravenous (IV) infusion to be given on Days 1 of Cycle 1 to 6 followed by post-induction treatment at a dose of 375 mg/m\^2 via IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than or equal to (\>/=) 18 years * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola + Len) treatment group: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator * For rituximab in combination with polatuzumab vedotin and lenalidomide (R + Pola + Len) treatment group: R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in patients who are not eligible for autologous stem-cell transplantation or who have experienced disease progression following treatment with high-dose chemotherapy plus autologous stem-cell transplantation * Histologically documented CD20-positive B-cell lymphoma as determined by the local laboratory * fluorodeoxyglucose (FDG)-avid lymphoma (i.e., positron emission tomography (PET)-positive lymphoma) * At least one bi-dimensionally measurable lesion * Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential
Exclusion criteria
* Grade 3b follicular lymphoma * History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL) * Known CD20-negative status at relapse or progression * Central nervous system (CNS) lymphoma or leptomeningeal infiltration * Prior allogeneic stem-cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1 * Current use of systemic immunosuppressant(s), or prior anti-cancer therapy to include: lenalidomide, fludarabine, or alemtuzumab within 12 months; radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1 * Active infection * Positive for human immunodeficiency virus (HIV) or hepatitis B or C * Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1 * Poor hematologic, renal, or hepatic function * Pregnant or lactating women * Life expectancy less than (\<) 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase | A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of \> 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase \> 3 x baseline and an increase in direct bilirubin \> 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Percentages have been rounded off to the first decimal point. |
| Percentage of Participants With Adverse Events (AEs) | From study start up to end of study (Up to a maximum of 69 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. Percentages have been rounded off to the first decimal point. |
| Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) | CR at EOI was assessed by IRC 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans | 6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks) | OR was defined as percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes & ELS with 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 & no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. Partial response (PR) based on PET-CT was defined as partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses 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). Percentages have been rounded off up to the second decimal point. |
| Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) | OR was defined percentage of participants with CR or PR assessed by the investigator according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes & ELS with score of 1, 2, 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 & no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses 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). Percentages are rounded off. |
| Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) | OR was defined as the percentage of participants with CR or PR, 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 in the 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 28 days). Percentages have been rounded off to the first decimal point. |
| Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) | OR was defined as the percentage of participants with CR or PR, 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 the 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. |
| Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months) | BOR=CR/PR per CT per MLRC. Per MLRC, CR based on CT was defined as a 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 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. Percentages have been rounded off to the first decimal point. |
| Observed Serum Obinutuzumab Concentration | Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months) | 1 cycle = 28 days |
| Observed Serum Rituximab Concentration | Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months) | — |
| Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) | CR at EOI was assessed by Investigator 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. |
| Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months) | — |
| Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months) | — |
| Observed Plasma Lenalidomide Concentration | Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months) | — |
| Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Baseline up to approximately 2 years after last dose (up to approximately 69 months) | The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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. |
| Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Baseline up to approximately 2 years after last dose (up to approximately 69 months) | The number of participants with positive results for HACAs, also called ADAs against rituximab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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. |
| Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months) | The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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. |
| Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months) | — |
| Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) | CR at EOI was determined by IRC 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 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. |
| Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone | 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks) | CR at EOI was determined by Investigator 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. |
Countries
Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 114 participants with relapsed or refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) were enrolled in this study at 28 investigative sites in Spain, United Kingdom, and United States from 24 March 2016 to 15 December 2021. The study consisted of two phases: dose-escalation and dose-expansion phase. All eligible participants in both phases received induction and post-induction therapy.
Pre-assignment details
Participants were enrolled in Phase Ib and Phase II study to receive polatuzumab vedotin (pola) in combination with lenalidomide (L) & fixed doses of rituximab (R)/obinutuzumab(G). Of the 114 enrolled participants, 113 participants received at least one dose of the study drug and their intended treatment. One participant withdrew consent prior to receiving any study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL Participants with FL received lenalidomide, 10 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months.
During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months. | 3 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL Participants with FL received lenalidomide, 10 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months.
During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months. | 4 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL Participants with FL received lenalidomide, 15 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months.
During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months. | 3 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL Participants with FL received lenalidomide, 20 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months.
During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months. | 6 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL Participants with DLBCL received lenalidomide, 10 mg, capsules orally QD on Days 1-21 of Cycles 1-6 (1 cycle = 28 days) along with rituximab, 375 milligrams per square meter (mg/m\^2), as IV infusion on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, as an IV infusion on Day 1 of Cycles 1 to 6, as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 6 months. During consolidation treatment, participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 6 months, and rituximab, 375 mg/m\^2 IV on Day 1 of every other month for up to 6 months. | 3 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL Participants with DLBCL received lenalidomide, 15 mg, capsules orally QD on Days 1-21 of Cycles 1-6 (1 cycle = 28 days) along with rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, as an IV infusion on Day 1 of Cycles 1 to 6, as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 6 months. During consolidation treatment, participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 6 months, and rituximab, 375 mg/m\^2 IV on Day 1 of every other month for up to 6 months. | 5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL Participants with DLBCL received lenalidomide, 20 mg, capsules orally QD on Days 1-21 of Cycles 1-6 (1 cycle = 28 days) along with rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, as an IV infusion on Day 1 of Cycles 1 to 6, as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 6 months. During consolidation treatment, participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 6 months, and rituximab, 375 mg/m\^2 IV on Day 1 of every other month for up to 6 months. | 10 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL Participants with FL received lenalidomide, 20 mg capsules orally QD on Days 1-21 of Cycles 1 to 6 (1 cycle = 28 days) along with obinutuzumab, 1000 mg, as IV infusion on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of Cycles 2-6, and polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of Cycles 1-6, as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months.
During maintenance treatment participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 12 months, and obinutuzumab, 1000 mg IV on Day 1 of every other month for up to 24 months. | 40 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL Participants with DLBCL received lenalidomide, 20 mg, capsules orally QD on Days 1-21 of Cycles 1-6 (1 cycle = 28 days) along with rituximab, 375 mg/m\^2, as IV infusion on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, as an IV infusion on Day 1 of Cycles 1 to 6, as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 6 months.
During consolidation treatment, participants received lenalidomide, 10 mg, capsules, orally, QD on Days 1-21 of each month (1 month = 28 days) for up to 6 months, and rituximab, 375 mg/m\^2 IV on Day 1 of every other month for up to 6 months. | 40 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 2 | 1 | 2 | 3 | 2 | 10 | 7 | 20 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Reason Not Specified | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 2 |
Baseline characteristics
| Characteristic | Total | Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 12.2 | 72.5 years STANDARD_DEVIATION 8.1 | 56.0 years STANDARD_DEVIATION 3.5 | 61.3 years STANDARD_DEVIATION 6.1 | 58.3 years STANDARD_DEVIATION 12 | 59.7 years STANDARD_DEVIATION 6.5 | 62.0 years STANDARD_DEVIATION 14.9 | 61.4 years STANDARD_DEVIATION 14.2 | 61.6 years STANDARD_DEVIATION 11.2 | 68.4 years STANDARD_DEVIATION 12.8 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 12 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 97 Participants | 4 Participants | 2 Participants | 3 Participants | 6 Participants | 3 Participants | 4 Participants | 7 Participants | 34 Participants | 34 Participants |
| Race/Ethnicity, Customized Ethnicity Not Stated | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 |
| 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 |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 108 Participants | 4 Participants | 3 Participants | 3 Participants | 6 Participants | 3 Participants | 5 Participants | 10 Participants | 36 Participants | 38 Participants |
| Sex: Female, Male Female | 42 Participants | 3 Participants | 2 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 4 Participants | 12 Participants | 14 Participants |
| Sex: Female, Male Male | 72 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 6 Participants | 28 Participants | 26 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 2 / 4 | 1 / 3 | 2 / 6 | 3 / 3 | 2 / 5 | 10 / 10 | 7 / 40 | 20 / 39 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 3 / 3 | 6 / 6 | 3 / 3 | 5 / 5 | 9 / 10 | 40 / 40 | 37 / 39 |
| serious Total, serious adverse events | 3 / 3 | 2 / 4 | 2 / 3 | 3 / 6 | 0 / 3 | 0 / 5 | 4 / 10 | 26 / 40 | 19 / 39 |
Outcome results
Primary
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. Percentages have been rounded off to the first decimal point.
Time frame: From study start up to end of study (Up to a maximum of 69 months)
Population: The safety-evaluable population included all participants who received at least one dose of any component of the combination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Percentage of Participants With Adverse Events (AEs) | 97.4 percentage of participants |
Primary
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
CR at EOI was assessed by IRC 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans | 66.7 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans | 0.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans | 60.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans | 38.5 percentage of participants |
Primary
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of \> 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase \> 3 x baseline and an increase in direct bilirubin \> 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Percentages have been rounded off to the first decimal point.
Time frame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase
Population: The safety-evaluable population included all participants who received at least one dose of any component of the combination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 50.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Percentage of Participants With Dose-Limiting Toxicities (DLTs) | 0.0 percentage of participants |
Secondary
Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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.
Time frame: Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months)
Population: Immunogenicity population included all safety-evaluable participants with at least one ADA sample. Due to missing baseline or post-baseline results not every participant was evaluable for baseline prevalence or post-baseline incidence of ADAs. 'Number Analyzed' is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 0 Participants |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 1 Participants |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Baseline prevalence of ADAs | 1 Participants |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin | Post baseline incidence of ADAs | 0 Participants |
Secondary
Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab
The number of participants with positive results for HACAs, also called ADAs against rituximab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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.
Time frame: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
Population: Immunogenicity population included all safety-evaluable participants with at least one ADA Sample. '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 (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab | Post baseline incidence of ADAs | 0 Participants |
Secondary
Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab
The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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.
Time frame: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
Population: Immunogenicity population included all safety-evaluable participants with at least one ADA Sample. '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 (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 0 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Baseline prevalence of ADAs | 3 Participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab | Post baseline incidence of ADAs | 0 Participants |
Secondary
Observed Plasma Lenalidomide Concentration
Time frame: Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)
Population: The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one 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 a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 35.0 ng/mL | Geometric Coefficient of Variation 109.1 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 118 ng/mL | Geometric Coefficient of Variation 44 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 124 ng/mL | Geometric Coefficient of Variation 21.4 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 5.97 ng/mL | Geometric Coefficient of Variation 628 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 64.0 ng/mL | Geometric Coefficient of Variation 1553.1 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 117 ng/mL | Geometric Coefficient of Variation 53.2 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 61.4 ng/mL | Geometric Coefficient of Variation 1354.8 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 96.4 ng/mL | Geometric Coefficient of Variation 62 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 40.8 ng/mL | Geometric Coefficient of Variation 183.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 0.729 ng/mL | Geometric Coefficient of Variation 540 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 65.7 ng/mL | Geometric Coefficient of Variation 46.3 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 76.1 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 29.2 ng/mL | Geometric Coefficient of Variation 55.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 93.3 ng/mL | Geometric Coefficient of Variation 40.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 1.95 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 144 ng/mL | Geometric Coefficient of Variation 30.3 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 56.8 ng/mL | Geometric Coefficient of Variation 57.2 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 179 ng/mL | Geometric Coefficient of Variation 220.1 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 116 ng/mL | Geometric Coefficient of Variation 28.9 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 8.74 ng/mL | Geometric Coefficient of Variation 277 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 201 ng/mL | Geometric Coefficient of Variation 54 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 202 ng/mL | Geometric Coefficient of Variation 36 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 189 ng/mL | Geometric Coefficient of Variation 48 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 110 ng/mL | Geometric Coefficient of Variation 35.1 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 227 ng/mL | Geometric Coefficient of Variation 48.1 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 305 ng/mL | Geometric Coefficient of Variation 37.1 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 272 ng/mL | Geometric Coefficient of Variation 48.2 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 5.20 ng/mL | Geometric Coefficient of Variation 275.1 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 49.8 ng/mL | Geometric Coefficient of Variation 23.3 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 152 ng/mL | Geometric Coefficient of Variation 36.9 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 202 ng/mL | Geometric Coefficient of Variation 115.6 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 200 ng/mL | Geometric Coefficient of Variation 45.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 12.5 ng/mL | Geometric Coefficient of Variation 76.4 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 44.0 ng/mL | Geometric Coefficient of Variation 40.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 5.43 ng/mL | Geometric Coefficient of Variation 9.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 25.2 ng/mL | Geometric Coefficient of Variation 239.4 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 118 ng/mL | Geometric Coefficient of Variation 22.3 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 69.9 ng/mL | Geometric Coefficient of Variation 10.3 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 36.2 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 79.9 ng/mL | Geometric Coefficient of Variation 28.2 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 224 ng/mL | Geometric Coefficient of Variation 76.8 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 237 ng/mL | Geometric Coefficient of Variation 47.4 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 2.64 ng/mL | Geometric Coefficient of Variation 68 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 41.7 ng/mL | Geometric Coefficient of Variation 546.7 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 232 ng/mL | Geometric Coefficient of Variation 25.5 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 134 ng/mL | Geometric Coefficient of Variation 23.6 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 57.0 ng/mL | Geometric Coefficient of Variation 19.1 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 258 ng/mL | Geometric Coefficient of Variation 10.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 73.3 ng/mL | Geometric Coefficient of Variation 395.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 197 ng/mL | Geometric Coefficient of Variation 184.1 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 328 ng/mL | Geometric Coefficient of Variation 38.2 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 8.33 ng/mL | Geometric Coefficient of Variation 112 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 105 ng/mL | Geometric Coefficient of Variation 50.9 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 187 ng/mL | Geometric Coefficient of Variation 150.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 255 ng/mL | Geometric Coefficient of Variation 36.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 245 ng/mL | Geometric Coefficient of Variation 36.3 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 237 ng/mL | Geometric Coefficient of Variation 52.1 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 124 ng/mL | Geometric Coefficient of Variation 300.3 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 214 ng/mL | Geometric Coefficient of Variation 41.1 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Unscheduled / 2h | 199 ng/mL | Geometric Coefficient of Variation 53.3 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 305 ng/mL | Geometric Coefficient of Variation 53.6 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 306 ng/mL | Geometric Coefficient of Variation 43.1 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 9.99 ng/mL | Geometric Coefficient of Variation 260.9 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 236 ng/mL | Geometric Coefficient of Variation 147.7 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 103 ng/mL | Geometric Coefficient of Variation 56.3 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 2h | 242 ng/mL | Geometric Coefficient of Variation 297.2 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 30 min | 94.5 ng/mL | Geometric Coefficient of Variation 204.9 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 4h | 205 ng/mL | Geometric Coefficient of Variation 45.4 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / Predose | 10.4 ng/mL | Geometric Coefficient of Variation 196.4 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 6 Day 1 / 2h | 153 ng/mL | Geometric Coefficient of Variation 515.5 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 8h | 103 ng/mL | Geometric Coefficient of Variation 67.6 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / 2h | 277 ng/mL | Geometric Coefficient of Variation 60 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Observed Plasma Lenalidomide Concentration | Induction Cycle 1 Day 15 / 1h | 245 ng/mL | Geometric Coefficient of Variation 106.8 |
Secondary
Observed Serum Obinutuzumab Concentration
1 cycle = 28 days
Time frame: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
Population: The pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one suitable postdose PK sample. '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 (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | EOI / Predose | 108 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 32.6 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 1 / Predose | 231 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 19.1 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / 30 mins | 103 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / 30 mins | 830 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 38.3 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / Predose | 451 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 23.5 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / 30 mins | 394 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 22.1 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / Predose | NA micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / 30 mins | 730 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 15.5 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / Predose | 354 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 15 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 29.1 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / Predose | 255 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 36.6 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 7 / Predose | 128 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 7 / Predose | 212 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / Predose | 372 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 37 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / 30 mins | 644 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 42.8 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / Predose | NA micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / Predose | 504 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 13 / Predose | 142 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / 30 mins | 804 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 19 / Predose | 354 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation | 46.4 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / 30 mins | 749 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 17.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 1 / Predose | 381 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / 30 mins | 358 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 20.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / Predose | 321 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 43.6 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / 30 mins | 695 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 14.3 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 7 / Predose | 229 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / 30 mins | 351 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 15.2 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / Predose | 386 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 4.6 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / Predose | NA micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / 30 mins | 1.18 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 19 / Predose | 204 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / Predose | 344 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 13.4 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | 1 Year Post Last Dose | 0.377 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / 30 mins | 653 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 20.6 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 13 / Predose | 269 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / Predose | 327 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 5.8 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / Predose | 384 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 52.2 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / Predose | NA micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / 30 mins | 333 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 70 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / Predose | 481 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 23.1 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / 30 mins | 667 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 77.5 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / Predose | 405 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 24.9 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / 30 mins | 742 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 27.8 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / 30 mins | 751 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 35.3 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 1 / Predose | 230 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 87.4 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 7 / Predose | 125 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 143.7 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 13 / Predose | 134 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 105.3 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Maintenance Month 19 / Predose | 154 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 144.1 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation | 17.3 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / Predose | 255 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 49 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / 30 mins | 547 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 37.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / Predose | NA micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Maintenance Month 13 / Predose | 150 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 70.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 4 Day 1 / Predose | 270 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 41.8 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / 30 mins | 588 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 41.4 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | 1 Year Post Last Dose | 0.340 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 955.9 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Maintenance Month 19 / Predose | 165 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 59.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 2 Day 1 / Predose | 312 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 40.8 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Unscheduled / Predose | 561 micrograms per milliliter (μg/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Study Drug Discontinuation | 87.5 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 588.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 1 Day 1 / 30 mins | 182 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 206.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Maintenance Month 1 / Predose | 176 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 60.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Induction Cycle 6 Day 1 / 30 mins | 543 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 36.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Day 120 Post Last Dose | 44.5 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 806.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Observed Serum Obinutuzumab Concentration | Maintenance Month 7 / Predose | 135 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 64.3 |
Secondary
Observed Serum Rituximab Concentration
Time frame: Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months)
Population: The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one 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 a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / 30 mins | 151 μg/mL | Geometric Coefficient of Variation 42.9 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / Predose | 25.6 μg/mL | Geometric Coefficient of Variation 78 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / 30 mins | 133 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / Predose | 20.4 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / 30 mins | 159 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / Predose | 15.3 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / 30 mins | 135 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / 30 mins | 224 μg/mL | Geometric Coefficient of Variation 5.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / Predose | 74.6 μg/mL | Geometric Coefficient of Variation 33.8 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / 30 mins | 203 μg/mL | Geometric Coefficient of Variation 28.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / 30 mins | 250 μg/mL | Geometric Coefficient of Variation 7.6 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / Predose | 79.5 μg/mL | Geometric Coefficient of Variation 42.3 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / 30 mins | 172 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / Predose | 33.3 μg/mL | Geometric Coefficient of Variation 43.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / Predose | 74.7 μg/mL | Geometric Coefficient of Variation 22.1 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / Predose | 31.7 μg/mL | Geometric Coefficient of Variation 26.2 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / 30 mins | 222 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / Predose | 53.1 μg/mL | Geometric Coefficient of Variation 43.7 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / 30 mins | 220 μg/mL | Geometric Coefficient of Variation 16.2 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / 30 mins | 233 μg/mL | Geometric Coefficient of Variation 1.8 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / 30 mins | 175 μg/mL | Geometric Coefficient of Variation 18.7 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / Predose | 26.4 μg/mL | Geometric Coefficient of Variation 73.4 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 2 Day 1 / 30 mins | 194 μg/mL | Geometric Coefficient of Variation 36.4 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / 30 mins | 174 μg/mL | Geometric Coefficient of Variation 45.4 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / Predose | 58.3 μg/mL | Geometric Coefficient of Variation 44.4 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / 30 mins | 256 μg/mL | Geometric Coefficient of Variation 26.4 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 6 Day 1 / Predose | 68.9 μg/mL | Geometric Coefficient of Variation 60.6 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Observed Serum Rituximab Concentration | Induction Cycle 4 Day 1 / 30 mins | 228 μg/mL | Geometric Coefficient of Variation 36.6 |
Secondary
Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
BOR=CR/PR per CT per MLRC. Per MLRC, CR based on CT was defined as a 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 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. Percentages have been rounded off to the first decimal point.
Time frame: Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 50.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 90.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone | 79.5 percentage of participants |
Secondary
Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone
CR at EOI was determined by Investigator 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM. 'Overall Number Analyzed'=number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone | 16.7 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone | 0.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone | 29.7 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone | 28.1 percentage of participants |
Secondary
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
CR at EOI was assessed by Investigator 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 66.7 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 0.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 60.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans | 33.3 percentage of participants |
Secondary
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
CR at EOI was determined by IRC 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 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM. 'Overall Number Analyzed'=number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 16.7 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 0.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 31.4 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone | 12.5 percentage of participants |
Secondary
Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans
OR was defined percentage of participants with CR or PR assessed by the investigator according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes & ELS with score of 1, 2, 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 & no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses 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). Percentages are rounded off.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans | 10.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans | 80.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans | 46.20 percentage of participants |
Secondary
Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone
OR was defined as the percentage of participants with CR or PR, 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 in the 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 28 days). Percentages have been rounded off to the first decimal point.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM. 'Overall Number Analyzed'=number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone | 12.5 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone | 91.4 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone | 53.1 percentage of participants |
Secondary
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone
OR was defined as the percentage of participants with CR or PR, 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 the 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM. 'Overall Number Analyzed'=number of participants with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone | 11.1 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone | 89.2 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone | 59.4 percentage of participants |
Secondary
Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans
OR was defined as percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes & ELS with 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 & no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. Partial response (PR) based on PET-CT was defined as partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses 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). Percentages have been rounded off up to the second decimal point.
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks)
Population: Efficacy-evaluable population=dose expansion participants who received atleast 1 dose of any component of the combination. As pre-specified in the protocol, data was collected and analysed only for participants in expansion phase arms \& those participants in dose-escalation arms who received study drugs at RP2D (i.e. arms: 1.4 mg Pola + 20 mg L+1000G for FL; 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL), for this OM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans | 100.0 percentage of participants |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans | 10.0 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans | 72.50 percentage of participants |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans | 46.20 percentage of participants |
Secondary
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
Time frame: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
Population: The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one 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 a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 50.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 7.3 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 580 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.6 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 4.96 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21.3 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 7.70 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 555 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 15.8 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 32.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 101980.7 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 5.34 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73.9 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Study Drug Discontinuation | 0.180 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 17.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 5.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 6.55 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 623 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.4 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Study Drug Discontinuation | 0.635 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 416 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 87.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 660 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 19.9 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 80.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17.6 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 24.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 13.8 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 11.5 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 508 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.7 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 2.50 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 483.1 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 519 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 9.3 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 8.47 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.5 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 9.37 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.6 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 0.961 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 477.5 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 476 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 16 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 11.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 232.2 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 9.70 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 53 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 531 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17.6 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 2.50 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 119.8 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 27.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69.2 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 295 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 174.6 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Study Drug Discontinuation | 0.180 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 7.68 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 60.8 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 6.73 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 118.8 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 432 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.9 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 3.06 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 568 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 58.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.4 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 22.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 7.44 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 537 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.3 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 4.19 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 371 nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 18.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.7 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 52.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.3 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 8.25 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 59.4 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 11.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.6 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 568 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 14.1 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 5.58 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 77.2 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 106 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 60902.6 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 507 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.8 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 6.12 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.1 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 716 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 16.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 18.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 11.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.2 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 43.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 96.4 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 737 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20.8 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 513 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 15.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.4 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 5.95 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 366.1 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 492 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.3 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 333 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 267.2 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 1.88 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 490.2 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 481 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.3 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Study Drug Discontinuation | 1.71 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 378.4 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 9.82 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.4 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Unscheduled / Predose | 23.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62.5 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 11.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 799 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 8.99 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.7 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / 30 mins | 522 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 323 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Unscheduled / Predose | 9.78 nanograms per milliliter (ng/mL) | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / 30 mins | 451 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 391.7 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / Predose | 11.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.2 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 4 Day 1 / 30 mins | 645 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 107.2 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 2 Day 1 / Predose | 5.32 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 103.6 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 15 | 16.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 118.6 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 6 Day 1 / Predose | 11.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 1 / Predose | NA nanograms per milliliter (ng/mL) | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) | Induction Cycle 1 Day 8 | 56.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 90.2 |
Secondary
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Time frame: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
Population: The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one 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 a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0431 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.228 ng/mL | Geometric Coefficient of Variation 7.8 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0280 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.151 ng/mL | Geometric Coefficient of Variation 68.6 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.0817 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0367 ng/mL | Geometric Coefficient of Variation 68.3 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.457 ng/mL | Geometric Coefficient of Variation 56.3 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Drug Discontinuation | 0.0180 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 1.15 ng/mL | Geometric Coefficient of Variation 34.9 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0929 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 2.05 ng/mL | Geometric Coefficient of Variation 49.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0315 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Drug Discontinuation | 0.0180 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.156 ng/mL | Geometric Coefficient of Variation 18.7 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.160 ng/mL | Geometric Coefficient of Variation 69.9 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.138 ng/mL | Geometric Coefficient of Variation 133 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.459 ng/mL | Geometric Coefficient of Variation 54.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.117 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.104 ng/mL | Geometric Coefficient of Variation 7.1 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.151 ng/mL | Geometric Coefficient of Variation 49.8 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.420 ng/mL | Geometric Coefficient of Variation 100.6 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0821 ng/mL | Geometric Coefficient of Variation 93.8 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 2.40 ng/mL | Geometric Coefficient of Variation 102 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.387 ng/mL | Geometric Coefficient of Variation 6 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0244 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0672 ng/mL | Geometric Coefficient of Variation 56.9 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0267 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0283 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.435 ng/mL | Geometric Coefficient of Variation 129.5 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.136 ng/mL | Geometric Coefficient of Variation 339.9 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.233 ng/mL | Geometric Coefficient of Variation 74 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Drug Discontinuation | 0.0180 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0334 ng/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 1.64 ng/mL | Geometric Coefficient of Variation 135.5 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.0752 ng/mL | Geometric Coefficient of Variation 113.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.156 ng/mL | Geometric Coefficient of Variation 62.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 1.89 ng/mL | Geometric Coefficient of Variation 76.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.186 ng/mL | Geometric Coefficient of Variation 51.2 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.485 ng/mL | Geometric Coefficient of Variation 204 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.0180 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0501 ng/mL | Geometric Coefficient of Variation 149 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0180 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0180 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0310 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.167 ng/mL | Geometric Coefficient of Variation 214.8 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 1.36 ng/mL | Geometric Coefficient of Variation 29.6 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.456 ng/mL | Geometric Coefficient of Variation 39.8 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.123 ng/mL | Geometric Coefficient of Variation 53.8 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0344 ng/mL | Geometric Coefficient of Variation 61 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.133 ng/mL | Geometric Coefficient of Variation 50.9 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0517 ng/mL | Geometric Coefficient of Variation 118.9 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.298 ng/mL | Geometric Coefficient of Variation 198.7 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0405 ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.683 ng/mL | Geometric Coefficient of Variation 63.3 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.157 ng/mL | Geometric Coefficient of Variation 72.5 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0729 ng/mL | Geometric Coefficient of Variation 11.4 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.208 ng/mL | Geometric Coefficient of Variation 44.9 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 3.65 ng/mL | Geometric Coefficient of Variation 75.3 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0527 ng/mL | Geometric Coefficient of Variation 102.8 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0268 ng/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.347 ng/mL | Geometric Coefficient of Variation 327.5 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 1.12 ng/mL | Geometric Coefficient of Variation 227 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.294 ng/mL | Geometric Coefficient of Variation 170.9 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Unscheduled / Predose | 0.180 ng/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0342 ng/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Study Drug Discontinuation | 0.0180 ng/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.102 ng/mL | Geometric Coefficient of Variation 57.7 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.102 ng/mL | Geometric Coefficient of Variation 101.2 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0366 ng/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / Predose | 0.0713 ng/mL | Geometric Coefficient of Variation 125 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 2 Day 1 / 30 mins | 0.210 ng/mL | Geometric Coefficient of Variation 77.3 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / Predose | 0.0776 ng/mL | Geometric Coefficient of Variation 101.5 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 15 | 0.843 ng/mL | Geometric Coefficient of Variation 125.2 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 8 | 2.56 ng/mL | Geometric Coefficient of Variation 144.8 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 4 Day 1 / 30 mins | 0.213 ng/mL | Geometric Coefficient of Variation 51.3 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / 30 mins | 0.297 ng/mL | Geometric Coefficient of Variation 111.1 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 1 Day 1 / Predose | NA ng/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Unscheduled / Predose | 0.0180 ng/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE | Induction Cycle 6 Day 1 / Predose | 0.0852 ng/mL | Geometric Coefficient of Variation 62.6 |
Secondary
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
Time frame: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
Population: The PK-evaluable population included all participants who received at least one dose of any component of the combination and who provided at least one 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 a specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 1.83 μg/mL | Geometric Coefficient of Variation 51.7 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Day 120 Post Last Dose | 0.0661 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | 1 Year Post Last Dose | 0.0250 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 1.47 μg/mL | Geometric Coefficient of Variation 16.2 |
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 0.106 μg/mL | Geometric Coefficient of Variation 209.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 2.01 μg/mL | Geometric Coefficient of Variation 51.1 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 0.170 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 4.45 μg/mL | Geometric Coefficient of Variation 20.5 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 2.57 μg/mL | Geometric Coefficient of Variation 30.5 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | 1 Year Post Last Dose | 0.0250 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 0.200 μg/mL | Geometric Coefficient of Variation 958.3 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 0.0903 μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 0.622 μg/mL | Geometric Coefficient of Variation 152.8 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 2.12 μg/mL | Geometric Coefficient of Variation 69 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 1.50 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 1.57 μg/mL | Geometric Coefficient of Variation 62.9 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 0.900 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 6.16 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Day 120 Post Last Dose | 0.208 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 1.61 μg/mL | Geometric Coefficient of Variation 59.8 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 2.96 μg/mL | Geometric Coefficient of Variation 44.4 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Day 120 Post Last Dose | 0.107 μg/mL | — |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 3.10 μg/mL | Geometric Coefficient of Variation 43.6 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 3.25 μg/mL | Geometric Coefficient of Variation 49.7 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 1.47 μg/mL | Geometric Coefficient of Variation 26.2 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 0.339 μg/mL | Geometric Coefficient of Variation 391.8 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 2.31 μg/mL | Geometric Coefficient of Variation 48.5 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 0.175 μg/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Day 120 Post Last Dose | 0.0365 μg/mL | — |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | 1 Year Post Last Dose | 0.0357 μg/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | 1 Year Post Last Dose | 0.0250 μg/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Day 120 Post Last Dose | 0.0666 μg/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 2 Day 1 / Predose | 1.35 μg/mL | Geometric Coefficient of Variation 122 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 1 Day 1 / Predose | NA μg/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Unscheduled / Predose | 2.59 μg/mL | — |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Study Drug Discontinuation | 0.455 μg/mL | Geometric Coefficient of Variation 448.4 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody | Induction Cycle 4 Day 1 / Predose | 3.42 μg/mL | Geometric Coefficient of Variation 46.1 |