Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination With Bendamustine and Rituximab Compared With Bendamustine and Rituximab Alone in Chinese Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL). (NCT NCT04236141)

Last Updated: 2023-03-03

Results Overview

CR was determined by IRC according to the Lugano Response Criteria (LRC) for Malignant Lymphoma. Per LRC , CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites 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 new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

42 participants

Primary outcome timeframe

Up to approximately 23 weeks

Results posted on

2023-03-03

Participant Flow

Participants took part in the study at 8 investigative sites in mainland China from 10 July 2020 to 07 February 2022.

A total of 42 participants were randomized in the study with a randomization ratio 2:1. Of the 42 participants randomized, 41 participants received at least one dose of study drug and their intended treatment.

Participant milestones

Participant milestones
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab Participants received polatuzumab vedotin administered at an initial dose of 1.8 milligrams per kilogram (mg/kg), as intravenous (IV) infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 milligrams per square meter (mg/m\^2), as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Overall Study STARTED	28	14
Overall Study Safety Population	27	14
Overall Study Pharmacokinetic-Evaluable Population	27	0
Overall Study Immunogenicity-Evaluable Population (Baseline Evaluable)	27	14
Overall Study Immunogenicity-Evaluable Population (Post-Baseline Evaluable)	24	0
Overall Study Intent-to-treat Population	28	14
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	28	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab Participants received polatuzumab vedotin administered at an initial dose of 1.8 milligrams per kilogram (mg/kg), as intravenous (IV) infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 milligrams per square meter (mg/m\^2), as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Overall Study Death	18	10
Overall Study Withdrawal by Participant	1	0
Overall Study Reason not Specified	1	0
Overall Study Study terminated by Sponsor	8	4

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination With Bendamustine and Rituximab Compared With Bendamustine and Rituximab Alone in Chinese Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.	Total n=42 Participants Total of all reporting groups
Age, Continuous	57.00 years n=5 Participants	60.50 years n=7 Participants	58.00 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	7 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants	14 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	28 Participants n=5 Participants	14 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC)	25.0 percentage of participants Interval 10.69 to 44.87	14.3 percentage of participants Interval 1.78 to 42.81

SECONDARY outcome

Timeframe: Up to approximately to 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

CR was determined by investigator according to the LRC for Malignant Lymphoma. Per LRC, CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites 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. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator	21.4 percentage of participants Interval 8.3 to 40.95	14.3 percentage of participants Interval 1.78 to 42.81

SECONDARY outcome

Timeframe: Up to approximately 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

OR was defined as CR or partial response (PR) at the end of treatment assessment based on PET-CT, as determined by the investigator according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites 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. PR based on PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal bone marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator	28.6 percentage of participants Interval 13.22 to 48.67	14.3 percentage of participants Interval 1.78 to 42.81

SECONDARY outcome

Timeframe: Up to approximately 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

OR was defined as CR or PR at the end of treatment assessment based on PET-CT, as determined by the IRC according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites 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. PR per PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1(1 cycle= 21 days) or after final dose of study treatment.Percentages have been rounded off to the first decimal point.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC	35.7 percentage of participants Interval 18.64 to 55.93	14.3 percentage of participants Interval 1.78 to 42.81

SECONDARY outcome

Timeframe: Up to approximately 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

CR was determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator	17.9 percentage of participants Interval 6.06 to 36.89	0 percentage of participants Interval 0.0 to 23.16

SECONDARY outcome

Timeframe: Up to approximately 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

CR was determined by the IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; 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 (1 cycle = 21 days) or after final dose of study treatment.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With CR at EOT Based on CT as Assessed by IRC	17.9 percentage of participants Interval 6.06 to 36.89	0 percentage of participants Interval 0.0 to 23.16

SECONDARY outcome

Timeframe: Up to approximately 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

OR was defined as CR or PR, at the EOT assessment based on CT only, as determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Per LRC, PR was defined as ≥ 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target nodes and extranodal sites; non-measured lesion is absent/normal, regressed, but no increase; spleen must have regressed by \>50 % in length beyond normal; and no new lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator	32.1 percentage of participants Interval 15.88 to 52.35	14.3 percentage of participants Interval 1.78 to 42.81

SECONDARY outcome

Timeframe: Up to approximately 23 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

OR was defined as percentage of participants with CR or PR, at EOT assessment based on CT only, as determined by IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi. PR is ≥ 50% decrease in SPD of up to 6 target nodes and extranodal sites. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC	28.6 percentage of participants Interval 13.22 to 48.67	14.3 percentage of participants Interval 1.78 to 42.81

SECONDARY outcome

Timeframe: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

BOR=CR/PR per PET-CT/CT by investigator per LRC.CR perPET-CT=complete MR in lymph nodes \& extralymphatic sites(ELS),score=1,2,3 with/without residual mass on5PS,1=no uptake(UT)above background;2=UT≤mediastinum;3=UT\>mediastinum but ≤liver;4=UT moderately\>liver;5=UT markedly higher than liver and/or new lesions; no new lesions \& FDG-avid disease absent in bone marrow.CR perCT=complete radiologic response with target nodes/nodal masses regressedto≤1.5 cm in LDi\&no ELS of disease;absence of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow morphology=normal,if indeterminate,IHC negative.PR per PET-CT=partial MR in lymph nodes\&ELS,score=4or5,reduced UT than baseline(BL)\&residual masses=any size;no new lesions\&residual UT \>UT in normal marrow,reduced than BL.PR per CT by LCR=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesion=absent/normal,regressed,no increase;spleen=regressed by\>50%in length beyond normal;no new lesions.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator	53.6 percentage of participants Interval 33.87 to 72.49	28.6 percentage of participants Interval 8.39 to 58.1

SECONDARY outcome

Timeframe: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

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

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC	53.6 percentage of participants Interval 33.87 to 72.49	50.0 percentage of participants Interval 23.04 to 76.96

SECONDARY outcome

Timeframe: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment. Overall number of participants analyzed are the number of BOR responders as assessed by investigator.

DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by the investigator according to the LRC

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=15 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=4 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator	5.45 months Interval 3.91 to 8.67	4.34 months Interval 2.6 to The upper limit of confidence interval (CI) was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)

DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by IRC according to the LRC.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=15 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=7 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
DOR Based on PET-CT/CT Only as Assessed by IRC	8.74 months Interval 3.55 to The upper limit of CI was not estimable due to insufficient number of participants with events.	4.27 months Interval 2.6 to The upper limit of CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 82 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by the investigator according to the LRC.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator	4.90 months Interval 3.12 to 6.6	2.00 months Interval 1.87 to 4.6

SECONDARY outcome

Timeframe: Up to approximately 82 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by IRC according to the LRC.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
PFS Based on PET-CT/CT Only as Assessed by IRC	5.42 months Interval 4.47 to The upper limit of CI was not estimable due to insufficient number of participants with events.	6.01 months Interval 3.52 to The upper limit of CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 82 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

EFS was defined as the time from date of randomization to any treatment failure including disease progression, relapse, initiation of new anti-lymphoma treatment (NALT), or death based on PET-CT or CT only, as determined by the investigator according to the LRC.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator	4.83 months Interval 3.12 to 6.44	2.00 months Interval 1.87 to 4.6

SECONDARY outcome

Timeframe: Up to approximately 82 weeks

Population: ITT population included all participants randomized, whether or not the participants received the assigned treatment.

OS was defined as the time from date of randomization until the date of death from any cause.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=28 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Overall Survival (OS)	10.89 months Interval 5.52 to 16.66	7.67 months Interval 6.01 to The upper limit of CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 82 weeks

Population: Safety population included all randomized participants who received at least one dose of the study drug.

An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=27 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab n=14 Participants Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Percentage of Participants With Adverse Events (AEs)	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Predose & post dose on Day 2 of Cycle 1,& post dose on Days 8 & 15 of Cycles 1& 3; predose & post dose on Day 1 of Cycles 2, 3 & 4; treatment completion/early discontinuation visit; follow-up visits at Months 3 &6 (1 cycle=21 days) up to approx. 46 weeks

Population: PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Number analyzed is the number of participants with data available for analysis at the specified time point.

PK of polatuzumab vedodtin-related analyte- total antibody was measured

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=27 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Serum Concentration of Total Antibody at Specified Timepoints Cycle 1 Day 2: Pre-dose	NA micrograms per milliliter (μg/mL) Geometric Coefficient of Variation NA The data is not evaluable as all samples were below the limit of quantification (BLQ).	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 1 Day 2: Post dose	41.5 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 26.3	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 1 Day 8 Post dose	9.83 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 38.3	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 1 Day 15 Post dose	5.42 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 35.6	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 2 Day 1: Pre-dose	3.13 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 37.3	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 2 Day 1: Post dose	49.1 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 39.6	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 3 Day 1: Pre-dose	4.30 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 36.3	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 3 Day 1: Post dose	45.6 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 28.9	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 3 Day 8 Post dose	13.6 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 29.1	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 3 Day 15 Post dose	8.48 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 30.8	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 4 Day 1: Pre-dose	5.37 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 52.5	—
Serum Concentration of Total Antibody at Specified Timepoints Cycle 4 Day 1: Post dose	47.2 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 34.8	—
Serum Concentration of Total Antibody at Specified Timepoints Treatment completion/Early discontinuation	4.44 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 49.5	—
Serum Concentration of Total Antibody at Specified Timepoints Follow-Up Month 3	0.182 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation NA Since more than one-third values were BLQ, the geometric coefficient of variation was not estimable.	—
Serum Concentration of Total Antibody at Specified Timepoints Follow-Up Month 6	0.0410 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation NA Since more than one-third values were BLQ, the geometric coefficient of variation was not estimable.	—

SECONDARY outcome

Timeframe: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks

PK of polatuzumab vedodtin-related analyte- acMMAE was measured.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=27 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 1 Day 2: Pre-dose	NA nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The data is not evaluable as all samples were BLQ.	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 1 Day 2: Post dose	560 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23.0	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 1 Day 8 Post dose	65.5 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 212.3	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 1 Day 15 Post dose	26.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 35.7	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 2 Day 1: Pre-dose	10.9 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 35.9	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 2 Day 1: Post dose	524 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 97.4	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 3 Day 1: Pre-dose	14.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 36.1	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 3 Day 1: Post dose	605 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 19.5	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 3 Day 8 Post dose	64.5 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 210.3	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 3 Day 15 Post dose	33.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 31.7	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 4 Day 1: Pre-dose	15.4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 56.2	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Cycle 4 Day 1: Post dose	602 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 19.4	—
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints Treatment completion/Early discontinuation	10.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 49.1	—

SECONDARY outcome

PK of polatuzumab vedodtin-related analyte- unconjugated MMAE was measured.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=27 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 1 Day 2: Pre-dose	NA ng/mL Geometric Coefficient of Variation NA The data is not evaluable as all samples were BLQ.	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 1 Day 2: Post dose	0.139 ng/mL Geometric Coefficient of Variation 81.9	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 1 Day 8 Post dose	2.47 ng/mL Geometric Coefficient of Variation 50.6	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 1 Day 15 Post dose	0.627 ng/mL Geometric Coefficient of Variation 64.1	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 2 Day 1: Pre-dose	0.0870 ng/mL Geometric Coefficient of Variation 106.8	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 2 Day 1: Post dose	0.127 ng/mL Geometric Coefficient of Variation 72.2	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 3 Day 1: Pre-dose	0.0944 ng/mL Geometric Coefficient of Variation 65.9	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 3 Day 1: Post dose	0.171 ng/mL Geometric Coefficient of Variation 44.1	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 3 Day 8 Post dose	1.49 ng/mL Geometric Coefficient of Variation 149.6	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 3 Day 15 Post dose	0.509 ng/mL Geometric Coefficient of Variation 58.7	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 4 Day 1: Pre-dose	0.0851 ng/mL Geometric Coefficient of Variation 130.9	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Cycle 4 Day 1: Post dose	0.152 ng/mL Geometric Coefficient of Variation 64.6	—
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints Treatment completion/Early discontinuation	0.0711 ng/mL Geometric Coefficient of Variation 98.0	—

SECONDARY outcome

Timeframe: Baseline up to approximately 39 weeks

Population: Immunogenicity-evaluable population (Post-Baseline Evaluable) included all participants with at least one evaluable post-baseline anti-drug antibody (ADA) sample.

Treatment Emergent ADA is (a) negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, OR (b) positive ADA result at baseline and one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result.

Outcome measures

Outcome measures
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=24 Participants Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.	Placebo Plus Bendamustine and Rituximab Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin	0 Participants	—

Adverse Events

Polatuzumab Vedotin Plus Bendamustine and Rituximab

Serious events: 12 serious events

Other events: 27 other events

Deaths: 18 deaths

Placebo Plus Bendamustine and Rituximab

Serious events: 3 serious events

Other events: 14 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Polatuzumab Vedotin Plus Bendamustine and Rituximab n=27 participants at risk Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days	Placebo Plus Bendamustine and Rituximab n=14 participants at risk Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.
Blood and lymphatic system disorders Myelosuppression	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/27 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	7.1% 1/14 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
General disorders Asthenia	0.00% 0/27 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	7.1% 1/14 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Infections and infestations Infection	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	18.5% 5/27 • Number of events 6 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Infections and infestations Septic shock	0.00% 0/27 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	7.1% 1/14 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femur fracture	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Investigations Platelet count decreased	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/27 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	7.1% 1/14 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Haematuria	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Renal and urinary disorders Hydronephrosis	3.7% 1/27 • Number of events 1 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	3.7% 1/27 • Number of events 2 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.	0.00% 0/14 • Up to approximately 82 weeks All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee "The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights."
Publication restrictions are in place

Restriction type: OTHER