Diffuse, Large B-Cell, Lymphoma
Conditions
Brief summary
A study to evaluate the Efficacy and Safety of Polatuzumab Vedotin in combination with BR (Bendamustine and Rituximab) compared with BR alone in Chinese participants with R/R DLBCL. Approximately 42 Chinese participants will be randomised to treatment arms in a 2:1 ratio. Randomisation will be conducted with the aid of an interactive web-based response system (IxRS).
Interventions
DRUGPolatuzumab Vedotin
Participants will receive a total of 6 cycles (a cycle being 21 days) of 1.8mg/kg Polatuzumab Vedotin (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.
DRUGBendamustine
Participants will receive a total of 6 cycles (a cycle being 21 days) of 90 mg/m2 Bendamustine (IV infusion) on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.
DRUGRituximab
Participants will receive a total of 6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab (IV infusion) on Day 1 of each cycle.
DRUGPlacebo
Participants will receive a total of 6 cycles (a cycle being 21 days) of Placebo (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to comply with the study protocol and procedures, in the investigator's judgement. * Transplant ineligible participants with R/R DLBCL. * Confirmed DLBCL diagnosis. * For participants who have received prior bendamustine, a response duration \> 1 year (for participants who have relapsed disease after a prior regimen). * At least one bi-dimensionally measurable lesion, defined as \> 1.5 cm in its longest dimension as measured by CT or magnetic resonance imaging (MRI). * Availability of archival or freshly collected tumor tissue before study enrolment. * Life expectancy of at least 24 weeks. * ECOG Performance Status of 0, 1 or 2. * Adequate haematologic function. * Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs. * For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm. * Residence in the People's Republic of China.
Exclusion criteria
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs) or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products. * Contraindication to bendamustine or rituximab. * History of sensitivity to mannitol (mannitol is an excipient in bendamustine). * Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 5 half-lives or 4 weeks, whichever is longer, before Cycle 1, Day 1. * Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1, Day 1. * Ongoing corticosteroid use \> 30 mg/day prednisone or equivalent, for purposes other than lymphoma symptom control. * Completion of autologous SCT within 100 days prior to Cycle 1, Day 1. * Prior allogeneic Stem Cell Transplantation (SCT). * Prior treatment with Chimeric Antigen Receptor (CAR) T-cell therapy. * Eligibility for autologous SCT. * Grade 3b Follicular Lymphoma (FL). * History of transformation of indolent disease to DLBCL. * Primary or secondary CNS lymphoma. * Current Grade \> 1 peripheral neuropathy. * History of other malignancy that could affect compliance with the protocol or interpretation of results. * Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular or pulmonary disease. * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1. * Participants with suspected or latent tuberculosis. * Positive Chronic Hepatitis B (HBV) infection or Hepatitis C (HCV) infection. * Known history of HIV infection. * Known infection human T-cell leukemia virus 1 virus. * Vaccination with a live vaccine within 28 days prior to treatment. * Recent major surgery (within 6 weeks before the start of Cycle 1, Day 1) other than for diagnosis. * Pregnant or breastfeeding or intending to become pregnant during the study or within 12 months after the final dose of study treatment. * Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC) | Up to approximately 23 weeks | CR was determined by IRC according to the Lugano Response Criteria (LRC) for Malignant Lymphoma. Per LRC , CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites 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 new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator | Up to approximately 23 weeks | OR was defined as CR or partial response (PR) at the end of treatment assessment based on PET-CT, as determined by the investigator according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. PR based on PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal bone marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. |
| Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC | Up to approximately 23 weeks | OR was defined as CR or PR at the end of treatment assessment based on PET-CT, as determined by the IRC according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. PR per PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1(1 cycle= 21 days) or after final dose of study treatment.Percentages have been rounded off to the first decimal point. |
| Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator | Up to approximately 23 weeks | CR was determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. |
| Percentage of Participants With CR at EOT Based on CT as Assessed by IRC | Up to approximately 23 weeks | CR was determined by the IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. |
| Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator | Up to approximately 23 weeks | OR was defined as CR or PR, at the EOT assessment based on CT only, as determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Per LRC, PR was defined as ≥ 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target nodes and extranodal sites; non-measured lesion is absent/normal, regressed, but no increase; spleen must have regressed by \>50 % in length beyond normal; and no new lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point. |
| Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC | Up to approximately 23 weeks | OR was defined as percentage of participants with CR or PR, at EOT assessment based on CT only, as determined by IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi. PR is ≥ 50% decrease in SPD of up to 6 target nodes and extranodal sites. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. |
| Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator | Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks) | BOR=CR/PR per PET-CT/CT by investigator per LRC.CR perPET-CT=complete MR in lymph nodes & extralymphatic sites(ELS),score=1,2,3 with/without residual mass on5PS,1=no uptake(UT)above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver and/or new lesions; no new lesions & FDG-avid disease absent in bone marrow.CR perCT=complete radiologic response with target nodes/nodal masses regressedto≤1.5 cm in LDi&no ELS of disease;absence of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow morphology=normal,if indeterminate,IHC negative.PR per PET-CT=partial MR in lymph nodes&ELS,score=4or5,reduced UT than baseline(BL)&residual masses=any size;no new lesions&residual UT \>UT in normal marrow,reduced than BL.PR per CT by LCR=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesion=absent/normal,regressed,no increase;spleen=regressed by\>50%in length beyond normal;no new lesions. |
| Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC | Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks) | BOR=CR/PR per PET-CT/CT by IRC per LRC. CR per PET-CT=complete MR in lymph nodes& ELS, score=1, 2,3 with/without residual mass on 5PS, 1=no UT above background; 2=UT≤mediastinum; 3=UT\>mediastinum but ≤liver; 4=UT moderately\>liver; 5=UT markedly higher than liver and/or new lesions; no new lesions & FDG-avid disease absent in bone marrow.CR per CT=complete radiologic response with target nodes/nodal masses regressed to≤1.5 cm in LDi and no ELS of disease; absence of non-measured lesion; organ enlargement regressed to normal; no new lesions; bone marrow morphology=normal, if indeterminate, IHC negative. PR per PET-CT=partial MR in lymph nodes & ELS, score =4 or 5,reduced UT than baseline(BL)&residual masses=any size; no new lesions &residual UT \>UT in normal marrow, reduced than BL.PR per CT by LCR=≥50% decrease in SPD of up to 6 target nodes& extranodal sites; non-measured lesion=absent/normal, regressed, no increase; spleen=regressed by\>50% in length beyond normal; no new lesions. |
| Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator | Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks) | DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by the investigator according to the LRC |
| Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator | Up to approximately to 23 weeks | CR was determined by investigator according to the LRC for Malignant Lymphoma. Per LRC, CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point. |
| Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator | Up to approximately 82 weeks | PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by the investigator according to the LRC. |
| PFS Based on PET-CT/CT Only as Assessed by IRC | Up to approximately 82 weeks | PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by IRC according to the LRC. |
| Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator | Up to approximately 82 weeks | EFS was defined as the time from date of randomization to any treatment failure including disease progression, relapse, initiation of new anti-lymphoma treatment (NALT), or death based on PET-CT or CT only, as determined by the investigator according to the LRC. |
| Overall Survival (OS) | Up to approximately 82 weeks | OS was defined as the time from date of randomization until the date of death from any cause. |
| Percentage of Participants With Adverse Events (AEs) | Up to approximately 82 weeks | An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment. |
| Serum Concentration of Total Antibody at Specified Timepoints | Predose & post dose on Day 2 of Cycle 1,& post dose on Days 8 & 15 of Cycles 1& 3; predose & post dose on Day 1 of Cycles 2, 3 & 4; treatment completion/early discontinuation visit; follow-up visits at Months 3 &6 (1 cycle=21 days) up to approx. 46 weeks | PK of polatuzumab vedodtin-related analyte- total antibody was measured |
| Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks | PK of polatuzumab vedodtin-related analyte- acMMAE was measured. |
| Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks | PK of polatuzumab vedodtin-related analyte- unconjugated MMAE was measured. |
| Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin | Baseline up to approximately 39 weeks | Treatment Emergent ADA is (a) negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, OR (b) positive ADA result at baseline and one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. |
| DOR Based on PET-CT/CT Only as Assessed by IRC | Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks) | DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by IRC according to the LRC. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 8 investigative sites in mainland China from 10 July 2020 to 07 February 2022.
Pre-assignment details
A total of 42 participants were randomized in the study with a randomization ratio 2:1. Of the 42 participants randomized, 41 participants received at least one dose of study drug and their intended treatment.
Participants by arm
| Arm | Count |
|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6.
Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days. | 28 |
| Placebo Plus Bendamustine and Rituximab Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6.
Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days. | 14 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 18 | 10 |
| Overall Study | Reason not Specified | 1 | 0 |
| Overall Study | Study terminated by Sponsor | 8 | 4 |
| Overall Study | Withdrawal by Participant | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Plus Bendamustine and Rituximab | Total | Polatuzumab Vedotin Plus Bendamustine and Rituximab |
|---|---|---|---|
| Age, Continuous | 60.50 years | 58.00 years | 57.00 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 42 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 42 Participants | 28 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 28 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 18 / 28 | 10 / 14 |
| other Total, other adverse events | 27 / 27 | 14 / 14 |
| serious Total, serious adverse events | 12 / 27 | 3 / 14 |
Outcome results
Primary
Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC)
CR was determined by IRC according to the Lugano Response Criteria (LRC) for Malignant Lymphoma. Per LRC , CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites 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 new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Time frame: Up to approximately 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC) | 25.0 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC) | 14.3 percentage of participants |
95% CI: [-19, 40.43]
Secondary
DOR Based on PET-CT/CT Only as Assessed by IRC
DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by IRC according to the LRC.
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment. Overall number of participants analyzed are the number of BOR responders assessed by IRC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | DOR Based on PET-CT/CT Only as Assessed by IRC | 8.74 months |
| Placebo Plus Bendamustine and Rituximab | DOR Based on PET-CT/CT Only as Assessed by IRC | 4.27 months |
Secondary
Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator
DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by the investigator according to the LRC
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment. Overall number of participants analyzed are the number of BOR responders as assessed by investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator | 5.45 months |
| Placebo Plus Bendamustine and Rituximab | Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator | 4.34 months |
Secondary
Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator
EFS was defined as the time from date of randomization to any treatment failure including disease progression, relapse, initiation of new anti-lymphoma treatment (NALT), or death based on PET-CT or CT only, as determined by the investigator according to the LRC.
Time frame: Up to approximately 82 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator | 4.83 months |
| Placebo Plus Bendamustine and Rituximab | Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator | 2.00 months |
Secondary
Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin
Treatment Emergent ADA is (a) negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, OR (b) positive ADA result at baseline and 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 39 weeks
Population: Immunogenicity-evaluable population (Post-Baseline Evaluable) included all participants with at least one evaluable post-baseline anti-drug antibody (ADA) sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin | 0 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from date of randomization until the date of death from any cause.
Time frame: Up to approximately 82 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Overall Survival (OS) | 10.89 months |
| Placebo Plus Bendamustine and Rituximab | Overall Survival (OS) | 7.67 months |
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Time frame: Up to approximately 82 weeks
Population: Safety population included all randomized participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
Secondary
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator
BOR=CR/PR per PET-CT/CT by investigator per LRC.CR perPET-CT=complete MR in lymph nodes & extralymphatic sites(ELS),score=1,2,3 with/without residual mass on5PS,1=no uptake(UT)above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver and/or new lesions; no new lesions & FDG-avid disease absent in bone marrow.CR perCT=complete radiologic response with target nodes/nodal masses regressedto≤1.5 cm in LDi&no ELS of disease;absence of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow morphology=normal,if indeterminate,IHC negative.PR per PET-CT=partial MR in lymph nodes&ELS,score=4or5,reduced UT than baseline(BL)&residual masses=any size;no new lesions&residual UT \>UT in normal marrow,reduced than BL.PR per CT by LCR=≥50% decrease in SPD of up to 6 target nodes & extranodal sites;non-measured lesion=absent/normal,regressed,no increase;spleen=regressed by\>50%in length beyond normal;no new lesions.
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator | 53.6 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator | 28.6 percentage of participants |
95% CI: [-10.38, 60.38]
Secondary
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC
BOR=CR/PR per PET-CT/CT by IRC per LRC. CR per PET-CT=complete MR in lymph nodes& ELS, score=1, 2,3 with/without residual mass on 5PS, 1=no UT above background; 2=UT≤mediastinum; 3=UT\>mediastinum but ≤liver; 4=UT moderately\>liver; 5=UT markedly higher than liver and/or new lesions; no new lesions & FDG-avid disease absent in bone marrow.CR per CT=complete radiologic response with target nodes/nodal masses regressed to≤1.5 cm in LDi and no ELS of disease; absence of non-measured lesion; organ enlargement regressed to normal; no new lesions; bone marrow morphology=normal, if indeterminate, IHC negative. PR per PET-CT=partial MR in lymph nodes & ELS, score =4 or 5,reduced UT than baseline(BL)&residual masses=any size; no new lesions &residual UT \>UT in normal marrow, reduced than BL.PR per CT by LCR=≥50% decrease in SPD of up to 6 target nodes& extranodal sites; non-measured lesion=absent/normal, regressed, no increase; spleen=regressed by\>50% in length beyond normal; no new lesions.
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC | 53.6 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC | 50.0 percentage of participants |
95% CI: [-33.84, 40.98]
Secondary
Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator
CR was determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Time frame: Up to approximately 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator | 17.9 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator | 0 percentage of participants |
95% CI: [-1.69, 37.4]
Secondary
Percentage of Participants With CR at EOT Based on CT as Assessed by IRC
CR was determined by the IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Time frame: Up to approximately 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With CR at EOT Based on CT as Assessed by IRC | 17.9 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With CR at EOT Based on CT as Assessed by IRC | 0 percentage of participants |
95% CI: [-1.69, 37.4]
Secondary
Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator
CR was determined by investigator according to the LRC for Malignant Lymphoma. Per LRC, CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point.
Time frame: Up to approximately to 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator | 21.4 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator | 14.3 percentage of participants |
95% CI: [-22.03, 36.31]
Secondary
Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator
OR was defined as CR or partial response (PR) at the end of treatment assessment based on PET-CT, as determined by the investigator according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. PR based on PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal bone marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Time frame: Up to approximately 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator | 28.6 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator | 14.3 percentage of participants |
95% CI: [-15.89, 44.46]
Secondary
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator
OR was defined as CR or PR, at the EOT assessment based on CT only, as determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Per LRC, PR was defined as ≥ 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target nodes and extranodal sites; non-measured lesion is absent/normal, regressed, but no increase; spleen must have regressed by \>50 % in length beyond normal; and no new lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point.
Time frame: Up to approximately 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator | 32.1 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator | 14.3 percentage of participants |
95% CI: [-12.7, 48.42]
Secondary
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC
OR was defined as percentage of participants with CR or PR, at EOT assessment based on CT only, as determined by IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi. PR is ≥ 50% decrease in SPD of up to 6 target nodes and extranodal sites. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Time frame: Up to approximately 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC | 28.6 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC | 14.3 percentage of participants |
95% CI: [-15.89, 44.46]
Secondary
Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC
OR was defined as CR or PR at the end of treatment assessment based on PET-CT, as determined by the IRC according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. PR per PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1(1 cycle= 21 days) or after final dose of study treatment.Percentages have been rounded off to the first decimal point.
Time frame: Up to approximately 23 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC | 35.7 percentage of participants |
| Placebo Plus Bendamustine and Rituximab | Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC | 14.3 percentage of participants |
95% CI: [-9.44, 52.3]
Secondary
PFS Based on PET-CT/CT Only as Assessed by IRC
PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by IRC according to the LRC.
Time frame: Up to approximately 82 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | PFS Based on PET-CT/CT Only as Assessed by IRC | 5.42 months |
| Placebo Plus Bendamustine and Rituximab | PFS Based on PET-CT/CT Only as Assessed by IRC | 6.01 months |
Secondary
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints
PK of polatuzumab vedodtin-related analyte- acMMAE was measured.
Time frame: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 1 Day 15 Post dose | 26.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.7 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 2 Day 1: Pre-dose | 10.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.9 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 2 Day 1: Post dose | 524 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 97.4 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 1 Day 2: Pre-dose | NA nanograms per milliliter (ng/mL) | — |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 1 Day 2: Post dose | 560 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 1 Day 8 Post dose | 65.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 212.3 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 3 Day 1: Pre-dose | 14.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.1 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 3 Day 1: Post dose | 605 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.5 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 3 Day 8 Post dose | 64.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 210.3 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 3 Day 15 Post dose | 33.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.7 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 4 Day 1: Pre-dose | 15.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.2 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Cycle 4 Day 1: Post dose | 602 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.4 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints | Treatment completion/Early discontinuation | 10.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.1 |
Secondary
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints
PK of polatuzumab vedodtin-related analyte- unconjugated MMAE was measured.
Time frame: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 3 Day 8 Post dose | 1.49 ng/mL | Geometric Coefficient of Variation 149.6 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 3 Day 15 Post dose | 0.509 ng/mL | Geometric Coefficient of Variation 58.7 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 4 Day 1: Pre-dose | 0.0851 ng/mL | Geometric Coefficient of Variation 130.9 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 4 Day 1: Post dose | 0.152 ng/mL | Geometric Coefficient of Variation 64.6 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 1 Day 2: Pre-dose | NA ng/mL | — |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 1 Day 2: Post dose | 0.139 ng/mL | Geometric Coefficient of Variation 81.9 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 1 Day 8 Post dose | 2.47 ng/mL | Geometric Coefficient of Variation 50.6 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 1 Day 15 Post dose | 0.627 ng/mL | Geometric Coefficient of Variation 64.1 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 2 Day 1: Pre-dose | 0.0870 ng/mL | Geometric Coefficient of Variation 106.8 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 2 Day 1: Post dose | 0.127 ng/mL | Geometric Coefficient of Variation 72.2 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 3 Day 1: Pre-dose | 0.0944 ng/mL | Geometric Coefficient of Variation 65.9 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Cycle 3 Day 1: Post dose | 0.171 ng/mL | Geometric Coefficient of Variation 44.1 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints | Treatment completion/Early discontinuation | 0.0711 ng/mL | Geometric Coefficient of Variation 98 |
Secondary
Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator
PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by the investigator according to the LRC.
Time frame: Up to approximately 82 weeks
Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator | 4.90 months |
| Placebo Plus Bendamustine and Rituximab | Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator | 2.00 months |
Secondary
Serum Concentration of Total Antibody at Specified Timepoints
PK of polatuzumab vedodtin-related analyte- total antibody was measured
Time frame: Predose & post dose on Day 2 of Cycle 1,& post dose on Days 8 & 15 of Cycles 1& 3; predose & post dose on Day 1 of Cycles 2, 3 & 4; treatment completion/early discontinuation visit; follow-up visits at Months 3 &6 (1 cycle=21 days) up to approx. 46 weeks
Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 4 Day 1: Pre-dose | 5.37 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 52.5 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 4 Day 1: Post dose | 47.2 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 34.8 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Treatment completion/Early discontinuation | 4.44 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 49.5 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 1 Day 2: Pre-dose | NA micrograms per milliliter (μg/mL) | — |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 1 Day 2: Post dose | 41.5 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 26.3 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 1 Day 8 Post dose | 9.83 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 38.3 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 1 Day 15 Post dose | 5.42 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 35.6 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 2 Day 1: Pre-dose | 3.13 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 37.3 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 2 Day 1: Post dose | 49.1 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 39.6 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 3 Day 1: Pre-dose | 4.30 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 36.3 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 3 Day 1: Post dose | 45.6 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 28.9 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 3 Day 8 Post dose | 13.6 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 29.1 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Cycle 3 Day 15 Post dose | 8.48 micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 30.8 |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Follow-Up Month 3 | 0.182 micrograms per milliliter (μg/mL) | — |
| Polatuzumab Vedotin Plus Bendamustine and Rituximab | Serum Concentration of Total Antibody at Specified Timepoints | Follow-Up Month 6 | 0.0410 micrograms per milliliter (μg/mL) | — |