A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of Pinatuzumab Vedotin (DCDT2980S) in Combination With Rituximab or Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab and a Non-Randomized Phase Ib/II Evaluation of Polatuzumab Vedotin in Combination With Obinutuzumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Genentech, Inc.
- Enrollment
- 231
- Locations
- 41
- Primary Endpoint
- Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Study Overview
Brief Summary
This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- •Life expectancy of at least 12 weeks
- •History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
- •Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment
- •Have a clinical indication for treatment as determined by the investigator
- •Must have at least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT scan or Magnetic Resonance Imaging [MRI])
Exclusion Criteria
- •Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start
- •Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start
- •Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to (</=) 2 prior study start
- •Completion of autologous stem cell transplant (SCT) within 100 days prior study start
- •Prior allogeneic SCT
- •Eligibility for autologous SCT (participants with r/r DLBCL)
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- •History of other malignancy that could affect compliance with the protocol or interpretation of results
- •Current or past history of central nervous system lymphoma
- •Current Grade >1 peripheral neuropathy
- •Vaccination with a live vaccine within 28 days prior to treatment
Arms & Interventions
Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
For the first 2 cycles, RTX 375 milligrams per square meter (mg/m^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Intervention: Pinatuzumab Vedotin (Drug)
Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
For the first 2 cycles, RTX 375 milligrams per square meter (mg/m^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Intervention: Polatuzumab Vedotin (Drug)
Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab
For the first 2 cycles, RTX 375 milligrams per square meter (mg/m^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Intervention: Rituximab (Drug)
Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
For the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Intervention: Pinatuzumab Vedotin (Drug)
Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
For the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Intervention: Polatuzumab Vedotin (Drug)
Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab
For the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).
Intervention: Rituximab (Drug)
Cohort C (FL): RTX + Polatuzumab
For the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 1.8 mg/kg will be administered by IV infusion on Day 2 to Cohort C participants (with r/r FL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, PD, or withdrawal from study.
Intervention: Polatuzumab Vedotin (Drug)
Cohort C (FL): RTX + Polatuzumab
For the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 1.8 mg/kg will be administered by IV infusion on Day 2 to Cohort C participants (with r/r FL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, PD, or withdrawal from study.
Intervention: Rituximab (Drug)
Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab
For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort E participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Intervention: Obinutuzumab (Drug)
Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab
For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort E participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Intervention: Polatuzumab Vedotin (Drug)
Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort G participants (with r/r FL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort G participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Intervention: Obinutuzumab (Drug)
Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort G participants (with r/r FL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort G participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Intervention: Polatuzumab Vedotin (Drug)
Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort H participants (with r/r DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort H participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Intervention: Obinutuzumab (Drug)
Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab
For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort H participants (with r/r DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort H participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.
Intervention: Polatuzumab Vedotin (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time Frame: Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments greater than or equal to (\>/=) 4 weeks after initial documentation. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as \>/=50 percent (%) decrease in sum of the products of greatest diameters (SPD) of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a \>/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. Participants with insufficient data to determine response were classified as non-responders.
Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time Frame: First occurrence of objective response up to PD/relapse or death due to any cause, whichever occurred first (up to approximately 3.5 years)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014). DOR was defined as the time from the initial documentation of a CR or PR to the time of PD or death. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as \>/=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a \>/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
Percentage of Participants With CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) Per Lugano 2014 Response Criteria: Cohorts E, G, and H
Time Frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to \[\</=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \</=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.
Secondary Outcomes
- Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years))
- Percentage of Participants Who Died Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)(Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years))
- Overall Survival (OS): Rituximab Containing Regimens (Arms A and B, Cohort C)(Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years))
- Number of Participants With Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin(Baseline, post-baseline (up to approximately 5.5 years))
- Number of Participants With ADA to Polatuzumab Vedotin(Baseline, post-baseline (up to approximately 5.5 years))
- Number of Participants With ADA to Obinutuzumab(Baseline, post-baseline (up to approximately 5.5 years))
- Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years))
- Percentage of Participants With CR at EOT Based on PET/CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)(6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks))
- Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)(6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks))
- Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by the Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)(6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks))
- Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)(6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks))
- Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)(6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks))
- Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)(6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks))
- Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)(6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks))
- Percentage of Participants With Best OR Based on PET/CT or CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)(Baseline up to disease progression or death, whichever occurred first (up to approximately 5.5 years))
- Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)(Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days))
- Maximum Observed Concentration (Cmax) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)(Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days))
- Systemic Clearance (CL) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)(Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days))
- Half-Life (t1/2) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)(Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description))
- Volume of Distribution at Steady State (Vss) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)(Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description))
- AUCinf of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUCinf of Antibody Conjugated Monomethyl Auristatin E (acMMAE) for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Area Under the Concentration-Time Curve From Time Zero To Last Measurable Concentration (AUClast) of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of acMMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Cmax of Obinutuzumab: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)(Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days))
- Overall Survival (OS): Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)(Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years))
- Percentage of Participants Who Died Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)(Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years))
- Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)(Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years))
- Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)(Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 5.5 years))