A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01691898

Acronym

ROMULUS

Enrollment

231

Registered

2012-09-25

Start date

2012-09-27

Completion date

2019-02-07

Last updated

2020-02-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diffuse Large B-Cell Lymphoma, Follicular Lymphoma

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).

Interventions

DRUGObinutuzumab

Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

DRUGPinatuzumab Vedotin

Pinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

DRUGPolatuzumab Vedotin

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

DRUGRituximab

RTX 375 mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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)	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)	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	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

Measure	Time frame	Description
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)	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 \>/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
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)	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 \>/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. PFS was defined as the time from the date of randomization to the date of PD or death from any cause, whichever occurred first. In absence of PD or death, PFS was censored at the date of the last tumor assessment. Participants with no post-baseline tumor assessment were censored on the date of randomization or date of enrollment. The median PFS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
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)	Percentage of participants who died due to any cause was reported.
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)	OS was defined as the time from the date of randomization or enrollment to the date of death from any cause. The median OS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
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)	Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR was defined as a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR was defined as a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. CR was defined as reduction of longest transverse diameter (LDi) of target nodes/nodal masses to less than or equal to (\</=) 1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. CR was defined as reduction of LDi of target nodes/nodal masses to \</=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to \</=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. PR was defined as \>/=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen by at least \>50% beyond normal; and no new lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to \</=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. PR was defined as \>/=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen by at least \>50% beyond normal; and no new lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT or CT scan. Best OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR was defined as a score 4 (uptake moderately \>liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
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)	AUCinf for rituximab was estimated from serum concentration data using non-compartmental analysis.
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)	Cmax for rituximab was estimated from serum concentration data using non-compartmental analysis.
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)	CL for rituximab was estimated from serum concentration data using non-compartmental analysis.
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)	t1/2 for rituximab was estimated from serum concentration data using non-compartmental analysis. Time Frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, & 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days).
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)	Vss for rituximab was estimated from serum concentration data using non-compartmental analysis. Time Frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, & 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days)
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 total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with Monomethyl Auristatin E (MMAE)-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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)	AUCinf of acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. Antibody conjugated MMAE is the total concentration of MMAE that was conjugated to the antibody.
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)	AUClast of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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 total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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 acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
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)	Cmax of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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 total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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)	AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
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)	AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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 total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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 acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
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)	Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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 total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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)	AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
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)	AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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 total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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 acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
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)	Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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 total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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)	AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
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)	AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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 total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
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 acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
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 Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
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)	Cmax of obinutuzumab was estimated from serum concentration data using non-compartmental analysis.
Number of Participants With Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin	Baseline, post-baseline (up to approximately 5.5 years)	Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against pinatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was 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 = a participant with 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 greater than the Baseline titer result.
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)	Percentage of participants who died due to any cause was reported.
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)	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 \>/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. PFS was defined as the time from the date of randomization to the date of PD or death from any cause, whichever occurred first. In absence of PD or death, PFS was censored at the date of the last tumor assessment. Participants with no post-baseline tumor assessment were censored on the date of randomization or date of enrollment. The median PFS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
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)	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 \>/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
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)	OS was defined as the time from the date of randomization or enrollment to the date of death from any cause. The median OS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
Number of Participants With ADA to Polatuzumab Vedotin	Baseline, post-baseline (up to approximately 5.5 years)	Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against polatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was 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 = a participant with 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 greater than the Baseline titer result.
Number of Participants With ADA to Obinutuzumab	Baseline, post-baseline (up to approximately 5.5 years)	Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against obinutuzumab at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was 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 = a participant with 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 greater than the Baseline titer result.

Countries

Canada, France, Germany, Italy, Netherlands, United States

Participant flow

Recruitment details

A total of 289 participants were screened, out of which, 231 participants were enrolled into the study.

Participants by arm

Arm	Count
Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab Participants with relapsed or refractory \[r/r\] FL and DLBCL received rituximab (RTX) at a dose of 375 milligrams per square meter (mg/m\^2) administered via intravenous (IV) infusion on Day 1 and pinatuzumab vedotin at a dose of 2.4 milligrams per kilogram (mg/kg) administered via IV infusion on Day 2 for the first 2 cycles. RTX and pinatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed disease progression (PD) were treated with RTX at 375 mg/m\^2 and polatuzumab vedotin at 2.4 mg/kg via 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, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).	63
Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab Participants with r/r FL and DLBCL received RTX at a dose of 375 mg/m\^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 2.4 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. RTX and polatuzumab were administered on the same day (Day 1) in subsequent cycles beginning with the third cycle, in the absence of any infusion-related adverse events. Participants who developed PD were treated with RTX at 375 mg/m\^2 and pinatuzumab vedotin at 2.4 mg/kg via 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, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (maximum 17 cycles on an every-21-day schedule).	59
Cohort C (FL): RTX + Polatuzumab Participants with r/r FL received RTX at a dose of 375 mg/m\^2 administered via IV infusion on Day 1 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first 2 cycles. In the absence of any infusion-related adverse events, RTX and polatuzumab were 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, disease progression, or withdrawal from study.	20
Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab Participants with r/r FL and DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.	9
Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab Participants with r/r FL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.	40
Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab Participants with r/r DLBCL received obinutuzumab at a dose of 1000 mg via IV infusion on Days 1, 8, 15 and polatuzumab vedotin at a dose of 1.8 mg/kg administered via IV infusion on Day 2 for the first cycle. In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin were administered on the same day (Day 1) in subsequent cycles beginning with the second cycle for up to a maximum of 8 cycles or significant toxicity, disease progression, or withdrawal from study.	40
Total	231

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	0	1	0	1	1	0
Overall Study	Death	34	32	6	3	8	31
Overall Study	Lost to Follow-up	3	1	0	0	1	0
Overall Study	Non-Compliance	0	0	0	0	1	0
Overall Study	Progression of Disease	1	2	1	0	0	1
Overall Study	Withdrawal by Subject	9	8	2	1	3	3

Baseline characteristics

Characteristic	Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab	Total	Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab	Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab	Cohort C (FL): RTX + Polatuzumab	Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab	Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	24 Participants	122 Participants	34 Participants	34 Participants	8 Participants	5 Participants	17 Participants
Age, Categorical Between 18 and 65 years	16 Participants	109 Participants	29 Participants	25 Participants	12 Participants	4 Participants	23 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	10 Participants	2 Participants	5 Participants	1 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants	189 Participants	48 Participants	44 Participants	19 Participants	9 Participants	33 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	32 Participants	13 Participants	10 Participants	0 Participants	0 Participants	7 Participants
Sex: Female, Male Female	18 Participants	95 Participants	27 Participants	24 Participants	8 Participants	2 Participants	16 Participants
Sex: Female, Male Male	22 Participants	136 Participants	36 Participants	35 Participants	12 Participants	7 Participants	24 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	35 / 63	33 / 59	6 / 20	4 / 9	8 / 40	32 / 40
other Total, other adverse events	63 / 63	58 / 59	20 / 20	9 / 9	37 / 40	38 / 40
serious Total, serious adverse events	27 / 63	21 / 59	8 / 20	3 / 9	9 / 40	18 / 40

Outcome results

Primary

Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)

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.

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)

Population: Rituximab Containing Regimens (Arms A and B, Cohort C): Analysis was performed on efficacy-evaluable population participants who achieved objective response.

Arm	Measure	Value (MEDIAN)
Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab	Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	6.24 months
Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab	Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	6.47 months
Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab	Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	13.37 months
Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab	Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	9.36 months
Cohort C (FL): RTX + Polatuzumab	Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)	12.85 months

Primary

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)

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.

Time frame: Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)

Population: Rituximab Containing Regimens (Arms A and B, Cohort C): Analysis was performed on efficacy-evaluable population, which included all participants with baseline measurable disease and at least one post-baseline tumor assessment after study treatment.

Arm	Measure	Value (NUMBER)
Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab	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)	59.5 percentage of participants
Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab	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)	61.9 percentage of participants
Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab	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)	53.8 percentage of participants
Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab	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)	70.0 percentage of participants
Cohort C (FL): RTX + Polatuzumab	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)	75.0 percentage of participants

Primary

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

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.

Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)

Population: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H): Analysis was performed on efficacy-evaluable population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (NUMBER)
Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab	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	0 percentage of participants
Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab	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	50.0 percentage of participants
Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab	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	35.3 percentage of participants
Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab	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	0 percentage of participants

Secondary

Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)

AUCinf for rituximab was estimated from serum concentration data using non-compartmental analysis.

Time frame: 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)

Population: Rituximab Containing Regimens (Arms A and B, Cohort C): Analysis was performed on all participants with measurable pharmacokinetic (PK) concentrations. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Arm A (DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	5640 day*micrograms (mcg)/milliliter (mL)	Standard Deviation 8320
Arm A (FL): RTX+Pinatuzumab,Then RTX+Polatuzumab	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	3350 day*micrograms (mcg)/milliliter (mL)	Standard Deviation 1180
Arm B (DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	4200 day*micrograms (mcg)/milliliter (mL)	Standard Deviation 2620
Arm B (FL): RTX+Polatuzumab,Then RTX+Pinatuzumab	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	3910 day*micrograms (mcg)/milliliter (mL)	Standard Deviation 2480
Cohort C (FL): RTX + Polatuzumab	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)	2660 day*micrograms (mcg)/milliliter (mL)	Standard Deviation 879

Secondary

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

AUClast of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.