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

Hoffmann-La Roche331 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

331

Conditions

Lymphoma

Interventions

BendamustineDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (62)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Clearview Cancer Institute

Huntsville, Alabama, United States

City of Hope National Medical Center

Duarte, California, United States

Univ of Colorado Canc Ctr

Aurora, Colorado, United States

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

Jacksonville, Florida, United States

Outcomes

Primary Outcomes

Phase Ib: Percentage of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).

Time frame: From the study start up to the end of the study (up to approximately 84 months)

Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Time frame: From Month 37 to Month 84 (up to approximately 47 months)

Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin

The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Time frame: Baseline up to approximately Month 24

Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Time frame: Baseline up to approximately Month 24

Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)

The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Time frame: From Month 37 to Month 84 (up to approximately 47 months)

Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)

CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Time frame: 6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)

Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms\*day per milliliters.

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks

Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Secondary Outcomes

Phase II: Percentage of Participants With AEs

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Time frame: From the study start up to the end of the study (up to approximately 84 months)

Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin

The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Time frame: Baseline to approximately Month 24

Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator

CR was assessed by investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. Bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator

CR was determined by investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimetres (cm) in in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC

CR was determined by IRC a at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator

BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN \& ELS, score=4 or 5, reduced UT than baseline (BL) \& residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.

Time frame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)

DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC

Time frame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)

DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator

DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.

Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)

DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC

DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT\> background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT\>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT\>UT in normal bone marrow but\<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.

Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)

DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator

PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)

DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC

PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)

Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator

CR was assessed by Investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately\>liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator

BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes \& ELS, score=4 or 5, reduced UT than BL \& residual mass of any size;residual UT\>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.

Time frame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])

Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC

Time frame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator

Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator

PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC

PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])

Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator

EFS was defined as time from randomization to disease progression or relapse, as assessed by the investigator or death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.

Time frame: From Month 37 to Month 84 (up to approximately 47 months)

Phase II NF Cohorts: Overall Survival (OS)

OS was defined as the time from the date of randomization or first treatment (for obinutuzumab arms) to the date of death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.

Time frame: From Month 37 to Month 84 (up to approximately 47 months)

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator

CR was determined by Investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC

CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)

Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).

Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)

Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE

PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time frame: Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE

PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Time frame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose

Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab

PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time frame: Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab

PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Time frame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose

Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time frame: Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Time frame: Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose

Plasma Concentration of Bendamustine

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H).

Time frame: Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose

Serum Concentration of Rituximab

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H).

Time frame: Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)

Serum Concentration of Obinutuzumab

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time frame: Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody and unconjugated MMAE were measured.

Time frame: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F

PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured.

Time frame: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day\*micrograms per milliliter \[day\*ug/mL\]).

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks

Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F

The TINAS is an 11-item questionnaire that assesses the severity of neuropathy-related symptoms in the last 24 hours. The 11 items assessed were: hot/burning sensations in hands/feet, sensations pins and needles arms/legs, numbness or tingling in hands/feet, sensations of electric shock, pain when touching cold things, cramps in hands/feet, discomfort when touching things, discomfort skin contact with something, trouble grasping small objects, trouble walking loss feeling legs/feet, difficulty balance loss feeling leg/feet. Each item was scored on a 0-10 scale, with 0 being the symptom is not present, and 10 being the symptom is as bad as the participant can imagine. Higher scores indicate more severe disease. Scores were averaged at each week.

Time frame: Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)