A Phase IB/II Study Evaluating The Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination With Rituximab (R) or Obinutuzumab (G) Plus Bendamustine (B) in Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 331
- 试验地点
- 62
- 主要终点
- Phase Ib: Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL
- •If the participant has received prior bendamustine, response duration must have been greater than (>) 1 year (for participants who have relapse disease after a prior regimen)
- •At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension
- •Confirmed availability of archival or freshly collected tumor tissue
- •The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review.
- •Life expectancy of at least 24 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Adequate hematological function unless inadequate function is due to underlying disease
排除标准
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs, or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
- •Contraindication to bendamustine, rituximab, or obinutuzumab
- •Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives before Cycle 1 Day 1
- •Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1
- •Ongoing corticosteroid use >30 mg per day prednisone or equivalent, for purposes other than lymphoma symptom control
- •Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1 Day 1
- •Prior allogeneic SCT
- •Eligibility for autologous SCT
- •Grade 3b FL
- •History of transformation of indolent disease to DLBCL
- •Primary or secondary CNS lymphoma
- •Current Grade >1 peripheral neuropathy
- •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1 Day 1
- •Suspected or latent tuberculosis
- •Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C virus (HCV) antibody
- •Known history of human immunodeficiency virus (HIV) seropositive status or known infection with human T-cell leukemia virus 1 (HTLV-1) virus
- •Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort
- •Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation function tests
- •Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle 1, Day 1
研究组 & 干预措施
Arm A (Phase II Randomization): Polatuzumab+BR in FL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
干预措施: Bendamustine (Drug)
Arm A (Phase II Randomization): Polatuzumab+BR in FL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Arm A (Phase II Randomization): Polatuzumab+BR in FL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
干预措施: Rituximab (Drug)
Arm B (Phase II Randomization): BR in FL
Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.
干预措施: Bendamustine (Drug)
Arm B (Phase II Randomization): BR in FL
Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.
干预措施: Rituximab (Drug)
Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Bendamustine (Drug)
Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Rituximab (Drug)
Arm D (Phase II Randomization): BR in DLBCL
Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.
干预措施: Bendamustine (Drug)
Arm D (Phase II Randomization): BR in DLBCL
Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.
干预措施: Rituximab (Drug)
Arm E (Phase II Expansion): Polatuzumab+BG in FL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
干预措施: Bendamustine (Drug)
Arm E (Phase II Expansion): Polatuzumab+BG in FL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
干预措施: Obinutuzumab (Drug)
Arm E (Phase II Expansion): Polatuzumab+BG in FL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
干预措施: Bendamustine (Drug)
Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
干预措施: Obinutuzumab (Drug)
Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Bendamustine (Drug)
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Rituximab (Drug)
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
干预措施: Bendamustine (Drug)
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL
Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
干预措施: Rituximab (Drug)
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
干预措施: Bendamustine (Drug)
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
干预措施: Obinutuzumab (Drug)
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
干预措施: Bendamustine (Drug)
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
干预措施: Obinutuzumab (Drug)
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL
Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
干预措施: Polatuzumab vedotin (Liquid) (Drug)
Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL
In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Bendamustine (Drug)
Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL
In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Rituximab (Drug)
Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL
In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Polatuzumab vedotin (Lyophilized) (Drug)
Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL
In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Bendamustine (Drug)
Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL
In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Rituximab (Drug)
Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL
In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
干预措施: Polatuzumab vedotin (Lyophilized) (Drug)
结局指标
主要结局
Phase Ib: Percentage of Participants With Adverse Events (AEs)
时间窗: From the study start up to the end of the study (up to approximately 84 months)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
时间窗: From Month 37 to Month 84 (up to approximately 47 months)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
时间窗: Baseline up to approximately Month 24
The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
时间窗: From Month 37 to Month 84 (up to approximately 47 months)
The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)
时间窗: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
时间窗: 6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
时间窗: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms\*day per milliliters.
Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
时间窗: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
时间窗: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)
Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
时间窗: Baseline up to approximately Month 24
The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
时间窗: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
次要结局
- Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator(Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months))
- Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE(Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months))
- Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab(Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months))
- Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab(Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose)
- Phase II: Percentage of Participants With AEs(From the study start up to the end of the study (up to approximately 84 months))
- Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin(Baseline to approximately Month 24)
- Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab(Baseline to approximately Month 24)
- DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC(Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months))
- Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks))
- Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks))
- Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator(Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months]))
- Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks))
- Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC(From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months]))
- Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator(From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months]))
- Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC(From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months]))
- DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator(From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months))
- DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC(From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months))
- DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator(From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months))
- DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC(From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months))
- Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks))
- Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC(Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months]))
- Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator(From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months]))
- Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks))
- Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks))
- Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: CL of Bendamustine and Rituximab in Arms B and D(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)(Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks)
- Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator(From Month 37 to Month 84 (up to approximately 47 months))
- Phase II NF Cohorts: Overall Survival (OS)(From Month 37 to Month 84 (up to approximately 47 months))
- Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks))
- Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks))
- Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC(6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks))
- Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE(Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose)
- Plasma Concentration of Bendamustine(Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose)
- Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE(Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose)
- Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)(Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks)
- Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)(Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks)
- Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE(Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months))
- Serum Concentration of Rituximab(Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months))
- Serum Concentration of Obinutuzumab(Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months))
- Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a(Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b(Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C(Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: Cmax of Bendamustine and Rituximab in Arms B and D(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F(Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: Vss of Bendamustine and Rituximab in Arms B and D(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F(Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts))
- Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)(Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks)
- Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F(Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall))