A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

Phase 1

Completed

Conditions: Lymphoma

Interventions: Drug: Bendamustine
Drug: Obinutuzumab
Drug: Polatuzumab vedotin (Liquid)
Drug: Polatuzumab vedotin (Lyophilized)
Drug: Rituximab

Registration Number: NCT02257567

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 331

Inclusion Criteria

Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL
If the participant has received prior bendamustine, response duration must have been greater than (>) 1 year (for participants who have relapse disease after a prior regimen)
At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension
Confirmed availability of archival or freshly collected tumor tissue
The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review.
Life expectancy of at least 24 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Adequate hematological function unless inadequate function is due to underlying disease

Exclusion Criteria

History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs, or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
Contraindication to bendamustine, rituximab, or obinutuzumab
Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives before Cycle 1 Day 1
Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1
Ongoing corticosteroid use >30 mg per day prednisone or equivalent, for purposes other than lymphoma symptom control
Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1 Day 1
Prior allogeneic SCT
Eligibility for autologous SCT
Grade 3b FL
History of transformation of indolent disease to DLBCL
Primary or secondary CNS lymphoma
Current Grade >1 peripheral neuropathy
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1 Day 1
Suspected or latent tuberculosis
Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C virus (HCV) antibody
Known history of human immunodeficiency virus (HIV) seropositive status or known infection with human T-cell leukemia virus 1 (HTLV-1) virus
Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort
Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation function tests
Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle 1, Day 1

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm E (Phase II Expansion): Polatuzumab+BG in FL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL	Polatuzumab vedotin (Lyophilized)	In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL	Polatuzumab vedotin (Lyophilized)	In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
Arm A (Phase II Randomization): Polatuzumab+BR in FL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
Arm A (Phase II Randomization): Polatuzumab+BR in FL	Rituximab	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL	Polatuzumab vedotin (Liquid)	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
Arm A (Phase II Randomization): Polatuzumab+BR in FL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
Arm B (Phase II Randomization): BR in FL	Bendamustine	Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.
Arm E (Phase II Expansion): Polatuzumab+BG in FL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
Arm B (Phase II Randomization): BR in FL	Rituximab	Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.
Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL	Rituximab	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
Arm D (Phase II Randomization): BR in DLBCL	Bendamustine	Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.
Arm D (Phase II Randomization): BR in DLBCL	Rituximab	Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.
Arm E (Phase II Expansion): Polatuzumab+BG in FL	Obinutuzumab	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL	Obinutuzumab	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL	Rituximab	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL	Rituximab	Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL	Bendamustine	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL	Obinutuzumab	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL	Obinutuzumab	Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL	Bendamustine	In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL	Rituximab	In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL	Bendamustine	In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL	Rituximab	In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.

Primary Outcome Measures

Name	Time	Method
Phase Ib: Percentage of Participants With Adverse Events (AEs)	From the study start up to the end of the study (up to approximately 84 months)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs	From Month 37 to Month 84 (up to approximately 47 months)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin	Baseline up to approximately Month 24	The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)	From Month 37 to Month 84 (up to approximately 47 months)	The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC	6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)	CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks	Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms\*day per milliliters.
Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)
Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab	Baseline up to approximately Month 24	The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Secondary Outcome Measures

Name	Time	Method
Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	CR was determined by investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimetres (cm) in in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).
Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator	Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)	BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN \& ELS, score=4 or 5, reduced UT than baseline (BL) \& residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE	Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)	PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab	Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)	PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab	Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose	PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Phase II: Percentage of Participants With AEs	From the study start up to the end of the study (up to approximately 84 months)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin	Baseline to approximately Month 24	The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab	Baseline to approximately Month 24	The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC	Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)	BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN \& ELS, score=4 or 5, reduced UT than baseline (BL) \& residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	CR was assessed by investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	CR was determined by IRC a at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately\>liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator	Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])	BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes \& ELS, score=4 or 5, reduced UT than BL \& residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. Bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC	From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])	DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator	From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])	PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC	From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])	PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator	From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)	DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC	From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)	DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator	From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)	PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC	From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)	PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)	CR was assessed by Investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC	Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])	BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes \& ELS, score=4 or 5, reduced UT than BL \& residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator	From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])	DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)	OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II: CL of Bendamustine and Rituximab in Arms B and D	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator	From Month 37 to Month 84 (up to approximately 47 months)	EFS was defined as time from randomization to disease progression or relapse, as assessed by the investigator or death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.
Phase II NF Cohorts: Overall Survival (OS)	From Month 37 to Month 84 (up to approximately 47 months)	OS was defined as the time from the date of randomization or first treatment (for obinutuzumab arms) to the date of death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)	CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)	CR was determined by Investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC	6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)	CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.
Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE	Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose	PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Plasma Concentration of Bendamustine	Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose	Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H).
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE	Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose	PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day\micrograms per milliliter \[day\ug/mL\]).
Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks	PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured.
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE	Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)	PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Serum Concentration of Rituximab	Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)	Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H).
Serum Concentration of Obinutuzumab	Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)	Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a	Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b	Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C	Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody and unconjugated MMAE were measured.
Phase II: Cmax of Bendamustine and Rituximab in Arms B and D	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F	Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured.
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Phase II: Vss of Bendamustine and Rituximab in Arms B and D	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F	Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)	Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks	PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F	Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)	The TINAS is an 11-item questionnaire that assesses the severity of neuropathy-related symptoms in the last 24 hours. The 11 items assessed were: hot/burning sensations in hands/feet, sensations pins and needles arms/legs, numbness or tingling in hands/feet, sensations of electric shock, pain when touching cold things, cramps in hands/feet, discomfort when touching things, discomfort skin contact with something, trouble grasping small objects, trouble walking loss feeling legs/feet, difficulty balance loss feeling leg/feet. Each item was scored on a 0-10 scale, with 0 being the symptom is not present, and 10 being the symptom is as bad as the participant can imagine. Higher scores indicate more severe disease. Scores were averaged at each week.

Trial Locations

Locations (62): UMC St. Radboud; Hematology
🇳🇱
Nijmegen, Netherlands
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Swedish Cancer Inst.
🇺🇸
Seattle, Washington, United States
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
🇮🇹
Brescia, Lombardia, Italy
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Queen Elizabeth II Health Sciences Centre; Oncology
🇨🇦
Halifax, Nova Scotia, Canada
Fakultní nemocnice Ostrava Klinika hematoonkologie
🇨🇿
Ostrava, Czechia
Weinberg CA Inst Franklin Sq
🇺🇸
Baltimore, Maryland, United States
Emory Univ Winship Cancer Inst
🇺🇸
Atlanta, Georgia, United States
Prince of Wales Hospital; Oncology
🇦🇺
Randwick, New South Wales, Australia
Hopital Maisonneuve- Rosemont; Oncology
🇨🇦
Montreal, Quebec, Canada
Adelaide Cancer Centre
🇦🇺
Kurralta Park, South Australia, Australia
BCCA-Vancouver Cancer Centre
🇨🇦
Vancouver, British Columbia, Canada
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
🇨🇿
Brno, Czechia
Centre Leon Berard; Departement Oncologie Medicale
🇫🇷
Lyon, France
CHU Lyon Sud - Service Hématologie
🇫🇷
Pierre Benite, France
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Abt. für Hämatologie und Onkologie
🇩🇪
Mainz, Germany
Centre Henri Becquerel; Hematologie
🇫🇷
Rouen, France
HELIOS Klinikum Erfurt - Innere Medizin - 4. Medizinische Klinik, Hämatologie
🇩🇪
Erfurt, Germany
Hospital Universitario la Paz; Servicio de Hematologia
🇪🇸
Madrid, Spain
Clearview Cancer Institute
🇺🇸
Huntsville, Alabama, United States
Gemeinschaftspraxis für Hämatologie und Onkologie
🇩🇪
Münster, Germany
Univ of Colorado Canc Ctr
🇺🇸
Aurora, Colorado, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
🇺🇸
Jacksonville, Florida, United States
Joliet Oncology-Hematology; Associates, Ltd.
🇺🇸
Joliet, Illinois, United States
Horizon Oncology Research, Inc.
🇺🇸
Lafayette, Indiana, United States
Regional Cancer Care Associates LLC - Morristown
🇺🇸
Morristown, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
West Clinic
🇺🇸
Germantown, Tennessee, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Northwest Medical Specialties
🇺🇸
Tacoma, Washington, United States
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
Monash Medical Centre; Haematology Research
🇦🇺
Clayton, Victoria, Australia
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Czechia
Chu Site Du Bocage;Hematologie Clinique
🇫🇷
Dijon, France
I Interni klinika; Vseobecna fakultni nemocnice
🇨🇿
Prague 2, Czechia
Centre Hospitalier Departemental Les Oudairies
🇫🇷
La Roche Sur Yon, France
CHU Saint Eloi; Service d'Hématologie Clinique
🇫🇷
Montpellier, France
Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale
🇩🇪
Regensburg, Germany
National Institute of Oncology, A Dept of Internal Medicine
🇭🇺
Budapest, Hungary
Joh. Wesling Klinikum Minden; Klinik fuer Hämatologie und Onkologie
🇩🇪
Minden, Germany
Semmelweis University, First Dept of Medicine
🇭🇺
Budapest, Hungary
Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia
🇮🇹
Milano, Lombardia, Italy
University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B
🇭🇺
Debrecen, Hungary
Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
🇮🇹
Napoli, Campania, Italy
Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
🇮🇹
Alessandria, Piemonte, Italy
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
🇪🇸
Barcelona, Spain
Hospital Clinic i Provincial de Barcelona; Hematology
🇪🇸
Barcelona, Spain
Ankara University; Hematology
🇹🇷
Ankara, Turkey
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
🇪🇸
Sevilla, Spain
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
🇪🇸
Salamanca, Spain
Ondokuzmayis University Medical Faculty Heamatology Department
🇹🇷
Samsun, Turkey
Karadeniz Technical Uni School of Medicine; Hematology
🇹🇷
Trabzon, Turkey
Dokuz Eylul Uni ; Hematology
🇹🇷
Izmir, Turkey
KINGS COLLEGE HOSPITAL; Commercial R&D Amendments, Kings Health Partners Clinical Trials Office
🇬🇧
London, United Kingdom
Christie Hospital Nhs Trust; Medical Oncology
🇬🇧
Manchester, United Kingdom
Southampton General Hospital; Somers Cancer Research Building
🇬🇧
Southampton, United Kingdom
Nottingham City Hospital; Dept of Haematology
🇬🇧
Nottingham, United Kingdom