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).

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04236141
• Collaborator: (none)
• Enrollment: 42
• Locations: 10
• Arms: 2
• Actual Duration (Months): 19
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

A study to evaluate the Efficacy and Safety of Polatuzumab Vedotin in combination with BR (Bendamustine and Rituximab) compared with BR alone in Chinese participants with R/R DLBCL. Approximately 42 Chinese participants will be randomised to treatment arms in a 2:1 ratio. Randomisation will be conducted with the aid of an interactive web-based response system (IxRS).

Condition or Disease	Intervention/Treatment	Phase
Diffuse, Large B-Cell, Lymphoma	Drug: Polatuzumab Vedotin; Drug: Bendamustine; Drug: Rituximab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled 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.
• Actual Study Start Date: Jul 10, 2020
• Actual Primary Completion Date: Jul 12, 2021
• Actual Study Completion Date: Feb 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Polatuzumab Vedotin plus BR	Drug: Polatuzumab Vedotin; Participants will receive a total of 6 cycles (a cycle being 21 days) of 1.8mg/kg Polatuzumab Vedotin (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.; Drug: Bendamustine; Participants will receive a total of 6 cycles (a cycle being 21 days) of 90 mg/m2 Bendamustine (IV infusion) on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.; Drug: Rituximab; Participants will receive a total of 6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab (IV infusion) on Day 1 of each cycle.
Active Comparator: Placebo plus BR	Drug: Bendamustine; Participants will receive a total of 6 cycles (a cycle being 21 days) of 90 mg/m2 Bendamustine (IV infusion) on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.; Drug: Rituximab; Participants will receive a total of 6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab (IV infusion) on Day 1 of each cycle.; Drug: Placebo; Participants will receive a total of 6 cycles (a cycle being 21 days) of Placebo (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.

Outcome Measures

Primary Outcome Measures

1. 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) [Up to approximately 23 weeks]

   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 (each cycle is 21 days) or after final dose of study treatment.

Secondary Outcome Measures

1. Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator [Up to approximately to 23 weeks]

   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 (each cycle is 21 days) or after final dose of study treatment.

2. Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator [Up to approximately 23 weeks]

   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 (each cycle is 21 days) or after final dose of study treatment.

3. Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC [Up to approximately 23 weeks]

   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 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 marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days) or after final dose of study treatment.

4. Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator [Up to approximately 23 weeks]

   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 (each cycle is 21 days) or after final dose of study treatment.

5. Percentage of Participants With CR at EOT Based on CT as Assessed by IRC [Up to approximately 23 weeks]

   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 (each cycle is 21 days) or after final dose of study treatment.

6. Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator [Up to approximately 23 weeks]

   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 (each cycle is 21 days) or after final dose of study treatment.

7. Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC [Up to approximately 23 weeks]

   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 (each cycle is 21 days) or after final dose of study treatment.

8. Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator [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)]

   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.

9. Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC [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)]

   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.

10. Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator [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 the investigator according to the LRC

11. DOR Based on PET-CT/CT Only as Assessed by IRC [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.

12. Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator [Up to approximately 82 weeks]

    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.

13. PFS Based on PET-CT/CT Only as Assessed by IRC [Up to approximately 82 weeks]

    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.

14. Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator [Up to approximately 82 weeks]

    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.

15. Overall Survival (OS) [Up to approximately 82 weeks]

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

16. Percentage of Participants With Adverse Events (AEs) [Up to approximately 82 weeks]

    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.

17. Serum Concentration of Total Antibody at Specified Timepoints [Days 2, 8 and 15 of Cycle 1; Cycle 2 Day 1; Days 1, 8 and 15 of Cycle 3; Cycle 4 Day 1; treatment completion/early discontinuation (each cycle = 21 days) up to approximately 19 weeks]

18. Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints [Days 2, 8 and 15 of Cycle 1; Cycle 2 Day 1; Days 1, 8 and 15 of Cycle 3; Cycle 4 Day 1; treatment completion/early discontinuation (each cycle = 21 days) up to approximately 19 weeks]

19. Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints [Days 2, 8 and 15 of Cycle 1; Cycle 2 Day 1; Days 1, 8 and 15 of Cycle 3; Cycle 4 Day 1; treatment completion/early discontinuation (each cycle = 21 days) up to approximately 19 weeks]

20. Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin [Baseline up to approximately 19 weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able to comply with the study protocol and procedures, in the investigator's judgement.

• Transplant ineligible participants with R/R DLBCL.

• Confirmed DLBCL diagnosis.

• For participants who have received prior bendamustine, a response duration > 1 year (for participants who have relapsed disease after a prior regimen).

• At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or magnetic resonance imaging (MRI).

• Availability of archival or freshly collected tumor tissue before study enrolment.

• Life expectancy of at least 24 weeks.

• ECOG Performance Status of 0, 1 or 2.

• Adequate haematologic function.

• Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.

• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm.

• Residence in the People's Republic of China.

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs) or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products.

• Contraindication to bendamustine or rituximab.

• History of sensitivity to mannitol (mannitol is an excipient in bendamustine).

• Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 5 half-lives or 4 weeks, whichever is longer, before Cycle 1, Day 1.

• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1, Day 1.

• Ongoing corticosteroid use > 30 mg/day prednisone or equivalent, for purposes other than lymphoma symptom control.

• Completion of autologous SCT within 100 days prior to Cycle 1, Day 1.

• Prior allogeneic Stem Cell Transplantation (SCT).

• Prior treatment with Chimeric Antigen Receptor (CAR) T-cell therapy.

• Eligibility for autologous SCT.

• Grade 3b Follicular Lymphoma (FL).

• History of transformation of indolent disease to DLBCL.

• Primary or secondary CNS lymphoma.

• Current Grade > 1 peripheral neuropathy.

• History of other malignancy that could affect compliance with the protocol or interpretation of results.

• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular or pulmonary disease.

• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1.

• Participants with suspected or latent tuberculosis.

• Positive Chronic Hepatitis B (HBV) infection or Hepatitis C (HCV) infection.

• Known history of HIV infection.

• Known infection human T-cell leukemia virus 1 virus.

• Vaccination with a live vaccine within 28 days prior to treatment.

• Recent major surgery (within 6 weeks before the start of Cycle 1, Day 1) other than for diagnosis.

• Pregnant or breastfeeding or intending to become pregnant during the study or within 12 months after the final dose of study treatment.

• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing		China	100142
2	West China Hospital, Sichuan University	Chengdu		China	610041
3	Sun Yet-sen University Cancer Center	Guangzhou		China	510060
4	Harbin Medical University Cancer Hospital	Harbin		China	150081
5	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City		China	210029
6	Jiangsu Cancer Hospital	Nanjing City		China	211100
7	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
8	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430023
9	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an		China	710061
10	Henan Cancer Hospital	Zhengzhou		China	450008

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - May 12, 2020
• Statistical Analysis Plan - Mar 8, 2021

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04236141
• Other Study ID Numbers: YO41543
• First Posted: Jan 22, 2020
• Last Update Posted: Aug 4, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Rituximab; Bendamustine Hydrochloride

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 8 investigative sites in mainland China from 10 July 2020 to 07 February 2022.
Pre-assignment Detail	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.

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	28	14
Safety Population	27	14
Pharmacokinetic-Evaluable Population	27	0
Immunogenicity-Evaluable Population (Baseline Evaluable)	27	14
Immunogenicity-Evaluable Population (Post-Baseline Evaluable)	24	0
COMPLETED	15	5
NOT COMPLETED	13	9

Baseline Characteristics

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	28	14	42
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57.00	60.50	58.00
Sex: Female, Male (Count of Participants)
Female	7 25%	7 50%	14 33.3%
Male	21 75%	7 50%	28 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	28 100%	14 100%	42 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	28 100%	14 100%	42 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	25.0 89.3%	14.3 102.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	10.71
	Confidence Interval	(2-Sided) 95%; -19.00 to 40.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator
Description	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 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately to 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	21.4 76.4%	14.3 102.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	7.14
	Confidence Interval	(2-Sided) 95%; -22.03 to 36.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator
Description	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 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	28.6 102.1%	14.3 102.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	14.29
	Confidence Interval	(2-Sided) 95%; -15.89 to 44.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC
Description	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 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 marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	35.7 127.5%	14.3 102.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	21.43
	Confidence Interval	(2-Sided) 95%; -9.44 to 52.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator
Description	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 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	17.9 63.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	17.86
	Confidence Interval	(2-Sided) 95%; -1.69 to 37.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With CR at EOT Based on CT as Assessed by IRC
Description	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 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	17.9 63.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	17.86
	Confidence Interval	(2-Sided) 95%; -1.69 to 37.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator
Description	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 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	32.1 114.6%	14.3 102.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	17.86
	Confidence Interval	(2-Sided) 95%; -12.70 to 48.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC
Description	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 (each cycle is 21 days) or after final dose of study treatment.
Time Frame	Up to approximately 23 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	28.6 102.1%	14.3 102.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	14.29
	Confidence Interval	(2-Sided) 95%; -15.89 to 44.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	53.6 191.4%	28.6 204.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	25.00
	Confidence Interval	(2-Sided) 95%; -10.38 to 60.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Number (95% Confidence Interval) [percentage of participants]	53.6 191.4%	50.0 357.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Polatuzumab Vedotin Plus Bendamustine and Rituximab, Placebo Plus Bendamustine and Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	3.57
	Confidence Interval	(2-Sided) 95%; -33.84 to 40.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator
Description	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
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	15	4
Median (95% Confidence Interval) [months]	4.63	4.34

12. Secondary Outcome

Title	DOR Based on PET-CT/CT Only as Assessed by IRC
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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 assessed by IRC.

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	15	7
Median (95% Confidence Interval) [months]	8.74	4.27

13. Secondary Outcome

Title	Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator
Description	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.
Time Frame	Up to approximately 82 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Median (95% Confidence Interval) [months]	4.63	2.00

14. Secondary Outcome

Title	PFS Based on PET-CT/CT Only as Assessed by IRC
Description	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.
Time Frame	Up to approximately 82 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Median (95% Confidence Interval) [months]	5.42	6.01

15. Secondary Outcome

Title	Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator
Description	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.
Time Frame	Up to approximately 82 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Median (95% Confidence Interval) [months]	4.63	2.00

16. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from date of randomization until the date of death from any cause.
Time Frame	Up to approximately 82 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	28	14
Median (95% Confidence Interval) [months]	10.58	6.51

17. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	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.
Time Frame	Up to approximately 82 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab	Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.	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.
Measure Participants	27	14
Number [percentage of participants]	100 357.1%	100 714.3%

18. Secondary Outcome

Title	Serum Concentration of Total Antibody at Specified Timepoints
Time Frame	Days 2, 8 and 15 of Cycle 1; Cycle 2 Day 1; Days 1, 8 and 15 of Cycle 3; Cycle 4 Day 1; treatment completion/early discontinuation (each cycle = 21 days) up to approximately 19 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab
Arm/Group Description	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.
Measure Participants	27
Cycle 1 Day 2: Pre-dose	NA (NA)
Cycle 1 Day 2: Post dose	41.5 (26.3)
Cycle 1 Day 8	9.83 (38.3)
Cycle 1 Day 15	5.42 (35.6)
Cycle 2 Day 1: Pre-dose	3.13 (37.3)
Cycle 2 Day 1: Post dose	49.1 (39.6)
Cycle 3 Day 1: Pre-dose	4.15 (36.4)
Cycle 3 Day 1: Post dose	45.4 (30.6)
Cycle 3 Day 8	12.8 (25.6)
Cycle 3 Day 15	8.05 (31.5)
Cycle 4 Day 1: Pre-dose	5.07 (59.6)
Cycle 4 Day 1: Post dose	47.5 (41.7)
Treatment completion/Early discontinuation	3.88 (49.3)

19. Secondary Outcome

Title	Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints
Time Frame	Days 2, 8 and 15 of Cycle 1; Cycle 2 Day 1; Days 1, 8 and 15 of Cycle 3; Cycle 4 Day 1; treatment completion/early discontinuation (each cycle = 21 days) up to approximately 19 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab
Arm/Group Description	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.
Measure Participants	27
Cycle 1 Day 2: Pre-dose	NA (NA)
Cycle 1 Day 2: Post dose	560 (23.0)
Cycle 1 Day 8	65.5 (212.3)
Cycle 1 Day 15	26.7 (35.7)
Cycle 2 Day 1: Pre-dose	10.9 (35.9)
Cycle 2 Day 1: Post dose	524 (97.4)
Cycle 3 Day 1: Pre-dose	14.3 (36.9)
Cycle 3 Day 1: Post dose	593 (20.1)
Cycle 3 Day 8	59.0 (253.5)
Cycle 3 Day 15	32.4 (30.6)
Cycle 4 Day 1: Pre-dose	14.4 (61.8)
Cycle 4 Day 1: Post dose	579 (20.7)
Treatment completion/Early discontinuation	9.38 (51.1)

20. Secondary Outcome

Title	Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints
Time Frame	Days 2, 8 and 15 of Cycle 1; Cycle 2 Day 1; Days 1, 8 and 15 of Cycle 3; Cycle 4 Day 1; treatment completion/early discontinuation (each cycle = 21 days) up to approximately 19 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab
Arm/Group Description	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.
Measure Participants	27
Cycle 1 Day 2: Pre-dose	NA (NA)
Cycle 1 Day 2: Post dose	0.139 (81.9)
Cycle 1 Day 8	2.47 (50.6)
Cycle 1 Day 15	0.627 (64.1)
Cycle 2 Day 1: Pre-dose	0.0870 (106.8)
Cycle 2 Day 1: Post dose	0.127 (72.2)
Cycle 3 Day 1: Pre-dose	0.100 (53.9)
Cycle 3 Day 1: Post dose	0.179 (42.3)
Cycle 3 Day 8	1.42 (162.6)
Cycle 3 Day 15	0.502 (48.5)
Cycle 4 Day 1: Pre-dose	0.0840 (132.4)
Cycle 4 Day 1: Post dose	0.145 (66.8)
Treatment completion/Early discontinuation	0.0592 (91.0)

21. Secondary Outcome

Title	Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin
Description	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.
Time Frame	Baseline up to approximately 19 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab
Arm/Group Description	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.
Measure Participants	24
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Up to approximately 82 weeks
Adverse Event Reporting Description	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.
Arm/Group Title	Polatuzumab Vedotin Plus Bendamustine and Rituximab		Placebo Plus Bendamustine and Rituximab
Arm/Group Description	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.		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.
All Cause Mortality
	Polatuzumab Vedotin Plus Bendamustine and Rituximab		Placebo Plus Bendamustine and Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/28 (39.3%)		9/14 (64.3%)
Serious Adverse Events
	Polatuzumab Vedotin Plus Bendamustine and Rituximab		Placebo Plus Bendamustine and Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/27 (44.4%)		3/14 (21.4%)
Blood and lymphatic system disorders
Myelosuppression	1/27 (3.7%)	1	0/14 (0%)	0
Thrombocytopenia	1/27 (3.7%)	1	0/14 (0%)	0
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	0/27 (0%)	0	1/14 (7.1%)	1
General disorders
Asthenia	0/27 (0%)	0	1/14 (7.1%)	1
Pyrexia	1/27 (3.7%)	1	0/14 (0%)	0
Infections and infestations
Infection	1/27 (3.7%)	1	0/14 (0%)	0
Pneumonia	5/27 (18.5%)	6	0/14 (0%)	0
Septic shock	0/27 (0%)	0	1/14 (7.1%)	1
Injury, poisoning and procedural complications
Femur fracture	1/27 (3.7%)	1	0/14 (0%)	0
Investigations
Platelet count decreased	1/27 (3.7%)	1	0/14 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/27 (0%)	0	1/14 (7.1%)	1
Renal and urinary disorders
Haematuria	1/27 (3.7%)	1	0/14 (0%)	0
Hydronephrosis	1/27 (3.7%)	1	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/27 (3.7%)	2	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Polatuzumab Vedotin Plus Bendamustine and Rituximab		Placebo Plus Bendamustine and Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/27 (96.3%)		14/14 (100%)
Blood and lymphatic system disorders
Anaemia	14/27 (51.9%)	26	3/14 (21.4%)	5
Leukocytosis	1/27 (3.7%)	1	1/14 (7.1%)	1
Leukopenia	3/27 (11.1%)	5	0/14 (0%)	0
Myelosuppression	0/27 (0%)	0	1/14 (7.1%)	1
Neutropenia	2/27 (7.4%)	2	2/14 (14.3%)	2
Thrombocytopenia	1/27 (3.7%)	1	1/14 (7.1%)	1
Cardiac disorders
Bradycardia	0/27 (0%)	0	1/14 (7.1%)	1
Palpitations	1/27 (3.7%)	2	1/14 (7.1%)	1
Sinus tachycardia	2/27 (7.4%)	2	1/14 (7.1%)	1
Ear and labyrinth disorders
Deafness	0/27 (0%)	0	1/14 (7.1%)	1
Tinnitus	2/27 (7.4%)	2	0/14 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/27 (7.4%)	3	0/14 (0%)	0
Abdominal pain upper	2/27 (7.4%)	2	0/14 (0%)	0
Constipation	3/27 (11.1%)	5	2/14 (14.3%)	3
Diarrhoea	6/27 (22.2%)	9	0/14 (0%)	0
Dry mouth	0/27 (0%)	0	1/14 (7.1%)	1
Nausea	11/27 (40.7%)	21	4/14 (28.6%)	7
Vomiting	10/27 (37%)	19	4/14 (28.6%)	5
General disorders
Asthenia	0/27 (0%)	0	1/14 (7.1%)	1
Chest discomfort	0/27 (0%)	0	2/14 (14.3%)	2
Fatigue	9/27 (33.3%)	12	5/14 (35.7%)	5
Malaise	2/27 (7.4%)	2	0/14 (0%)	0
Oedema peripheral	2/27 (7.4%)	2	0/14 (0%)	0
Pyrexia	10/27 (37%)	14	1/14 (7.1%)	1
Hepatobiliary disorders
Hepatic function abnormal	0/27 (0%)	0	1/14 (7.1%)	1
Infections and infestations
Herpes zoster	2/27 (7.4%)	2	0/14 (0%)	0
Upper respiratory tract infection	1/27 (3.7%)	1	2/14 (14.3%)	2
Investigations
Alanine aminotransferase increased	8/27 (29.6%)	13	1/14 (7.1%)	1
Aspartate aminotransferase increased	6/27 (22.2%)	12	1/14 (7.1%)	3
Bilirubin conjugated increased	1/27 (3.7%)	1	1/14 (7.1%)	1
Blood bilirubin decreased	0/27 (0%)	0	1/14 (7.1%)	2
Blood bilirubin increased	2/27 (7.4%)	2	1/14 (7.1%)	1
Blood creatinine increased	5/27 (18.5%)	7	0/14 (0%)	0
Blood lactate dehydrogenase increased	5/27 (18.5%)	7	0/14 (0%)	0
Blood potassium decreased	2/27 (7.4%)	3	0/14 (0%)	0
Blood pressure increased	0/27 (0%)	0	1/14 (7.1%)	1
Blood uric acid increased	2/27 (7.4%)	3	0/14 (0%)	0
C-reactive protein increased	3/27 (11.1%)	3	0/14 (0%)	0
Electrocardiogram high voltage	1/27 (3.7%)	1	1/14 (7.1%)	1
Gamma-glutamyltransferase increased	3/27 (11.1%)	4	1/14 (7.1%)	1
Haemoglobin decreased	2/27 (7.4%)	2	0/14 (0%)	0
Lymphocyte count decreased	8/27 (29.6%)	13	10/14 (71.4%)	11
Lymphocyte percentage decreased	1/27 (3.7%)	2	1/14 (7.1%)	1
Mononuclear cell count increased	1/27 (3.7%)	2	1/14 (7.1%)	1
Neutrophil count decreased	17/27 (63%)	46	7/14 (50%)	14
Neutrophil count increased	2/27 (7.4%)	2	0/14 (0%)	0
Neutrophil percentage increased	1/27 (3.7%)	2	1/14 (7.1%)	1
Platelet count decreased	15/27 (55.6%)	24	6/14 (42.9%)	7
Protein urine present	2/27 (7.4%)	2	0/14 (0%)	0
Urine output decreased	0/27 (0%)	0	1/14 (7.1%)	1
Weight decreased	3/27 (11.1%)	3	1/14 (7.1%)	1
White blood cell count decreased	18/27 (66.7%)	50	9/14 (64.3%)	18
White blood cell count increased	2/27 (7.4%)	2	0/14 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	6/27 (22.2%)	10	2/14 (14.3%)	2
Hyperlipidaemia	5/27 (18.5%)	6	1/14 (7.1%)	1
Hyperuricaemia	3/27 (11.1%)	7	2/14 (14.3%)	2
Hypoalbuminaemia	3/27 (11.1%)	4	2/14 (14.3%)	2
Hypocalcaemia	2/27 (7.4%)	3	1/14 (7.1%)	1
Hypokalaemia	10/27 (37%)	21	4/14 (28.6%)	5
Hyponatraemia	4/27 (14.8%)	6	2/14 (14.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	0/27 (0%)	0	2/14 (14.3%)	2
Spinal pain	0/27 (0%)	0	1/14 (7.1%)	1
Nervous system disorders
Dizziness	0/27 (0%)	0	1/14 (7.1%)	1
Dysgeusia	0/27 (0%)	0	1/14 (7.1%)	1
Neuropathy peripheral	4/27 (14.8%)	4	1/14 (7.1%)	1
Paraesthesia	2/27 (7.4%)	2	0/14 (0%)	0
Psychiatric disorders
Insomnia	0/27 (0%)	0	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/27 (11.1%)	3	1/14 (7.1%)	1
Dyspnoea	0/27 (0%)	0	1/14 (7.1%)	1
Oropharyngeal pain	0/27 (0%)	0	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Pruritus	3/27 (11.1%)	4	1/14 (7.1%)	1
Rash	2/27 (7.4%)	3	2/14 (14.3%)	2
Urticaria	0/27 (0%)	0	1/14 (7.1%)	1
Vascular disorders
Hypertension	3/27 (11.1%)	3	0/14 (0%)	0
Hypotension	3/27 (11.1%)	3	0/14 (0%)	0
Venous thrombosis	3/27 (11.1%)	3	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

"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."