Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab, Gemcitabine and Oxaliplatin Compared to Rituximab, Gemcitabine and Oxaliplatin Alone in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (NCT NCT04182204)

NCT ID: NCT04182204

Last Updated: 2025-12-22

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

270 participants

Primary outcome timeframe

From treatment initiation until 90 days after the last dose of study drug or initiation of non-protocol-specified anti-lymphoma treatment (NALT) (Up to approximately 8.3 months)

Results posted on

2025-12-22

Participant Flow

A total of 270 participants with relapsed/refractory (r/r) diffuse large b-cell lymphoma (DLBCL) took part in the study at 64 investigative sites in 16 countries from 07 February 2020 to 29 November 2024.

The study was divided into 2 stages: Stage 1, or safety run-in (SRI), and Stage 2, or randomized controlled trial (RCT). Participants received polatuzumab vedotin in combination with rituximab + gemcitabine + oxaliplatin (Pola-R-GemOx) during the SRI stage. Participants were randomized in a 1:1 ratio to receive either Pola-R-GemOx or rituximab + gemcitabine + oxaliplatin (R-GemOx) in the RCT stage.

Participant milestones

Participant milestones
Measure	Stage 1: Pola-R-GemOx Participants received rituximab, 375 milligrams per square meter (mg/m\^2), intravenously (IV), followed by polatuzumab vedotin, 1.8 milligrams per kilogram (mg/kg), IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Safety Run-in STARTED	15	0	0
Safety Run-in COMPLETED	5	0	0
Safety Run-in NOT COMPLETED	10	0	0
Randomized Controlled Trial STARTED	0	126	129
Randomized Controlled Trial Safety-evaluable Population	0	125	128
Randomized Controlled Trial COMPLETED	0	32	55
Randomized Controlled Trial NOT COMPLETED	0	94	74

Reasons for withdrawal

Reasons for withdrawal
Measure	Stage 1: Pola-R-GemOx Participants received rituximab, 375 milligrams per square meter (mg/m\^2), intravenously (IV), followed by polatuzumab vedotin, 1.8 milligrams per kilogram (mg/kg), IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Safety Run-in Lost to Follow-up	1	0	0
Safety Run-in Withdrawal by Subject	2	0	0
Safety Run-in Death	7	0	0
Randomized Controlled Trial Lost to Follow-up	0	1	2
Randomized Controlled Trial Withdrawal by Subject	0	10	6
Randomized Controlled Trial Death	0	83	66

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab, Gemcitabine and Oxaliplatin Compared to Rituximab, Gemcitabine and Oxaliplatin Alone in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stage 1: Pola-R-GemOx n=15 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Total n=270 Participants Total of all reporting groups
Age, Continuous	70.7 years STANDARD_DEVIATION 12.6 • n=18 Participants	62.2 years STANDARD_DEVIATION 13.9 • n=102 Participants	63.0 years STANDARD_DEVIATION 14.5 • n=30 Participants	63.1 years STANDARD_DEVIATION 14.2 • n=37 Participants
Sex: Female, Male Female	7 Participants n=18 Participants	65 Participants n=102 Participants	56 Participants n=30 Participants	128 Participants n=37 Participants
Sex: Female, Male Male	8 Participants n=18 Participants	61 Participants n=102 Participants	73 Participants n=30 Participants	142 Participants n=37 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=18 Participants	26 Participants n=102 Participants	27 Participants n=30 Participants	54 Participants n=37 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=18 Participants	90 Participants n=102 Participants	97 Participants n=30 Participants	200 Participants n=37 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=18 Participants	10 Participants n=102 Participants	5 Participants n=30 Participants	16 Participants n=37 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=18 Participants	9 Participants n=102 Participants	7 Participants n=30 Participants	16 Participants n=37 Participants
Race/Ethnicity, Customized Asian	1 Participants n=18 Participants	41 Participants n=102 Participants	49 Participants n=30 Participants	91 Participants n=37 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=18 Participants	6 Participants n=102 Participants	3 Participants n=30 Participants	9 Participants n=37 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants
Race/Ethnicity, Customized White	14 Participants n=18 Participants	56 Participants n=102 Participants	60 Participants n=30 Participants	130 Participants n=37 Participants
Race/Ethnicity, Customized Other	0 Participants n=18 Participants	6 Participants n=102 Participants	8 Participants n=30 Participants	14 Participants n=37 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=18 Participants	8 Participants n=102 Participants	2 Participants n=30 Participants	10 Participants n=37 Participants

PRIMARY outcome

Timeframe: From treatment initiation until 90 days after the last dose of study drug or initiation of non-protocol-specified anti-lymphoma treatment (NALT) (Up to approximately 8.3 months)

Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1: Number of Participants With Adverse Events (AEs)	—	14 Participants	—

PRIMARY outcome

Timeframe: From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (Up to approximately 8.3 months)

Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage.

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1: Number of Participants With Peripheral Neuropathy (PN)	—	8 Participants	—

PRIMARY outcome

Timeframe: From randomization to death (Up to approximately 34 months)

Population: ITT population included all randomized participants.

OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. Kaplan-Meier (KM) method was used to estimate median OS for each treatment arm.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Overall Survival (OS)	19.5 months Interval 13.3 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	12.5 months Interval 8.9 to 15.8	—

SECONDARY outcome

Timeframe: From randomization to first occurrence of PD or death (Up to approximately 34 months)

Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.

PFS=time from randomization to the first occurrence of disease progression (PD) (based on either: PET-CT data/not including any PET data), as determined by investigator, per Lugano response criteria or death due to any cause, whichever occurs first. PD based on PET-CT data=score 4 (uptake moderately \> liver) or 5 (uptake markedly higher than liver \&/or new lesions) on 5-point scale (5PS) with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New/recurrent FDG-avid foci. Participants who did not report PD nor died at time of analysis were censored on the date of last evaluable tumor assessment if post-baseline tumor assessment or on date of randomization if no post-baseline tumor assessment. KM methodology was used to estimate median PFS.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=126 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: Progression-free Survival (PFS)	2.7 months Interval 2.4 to 3.3	3.9 months Interval 3.0 to 6.3	7.4 months Interval 6.2 to 11.7

SECONDARY outcome

Timeframe: Up to approximately 8.5 months

Population: ITT population included all randomized participants.

CRR was defined as the percentage of participants who had a complete metabolic response (CMR) based on positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by IRC. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \>mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Percentages are rounded off.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment	40.3 percentage of participants Interval 31.77 to 49.3	19.0 percentage of participants Interval 12.6 to 27.0	—

SECONDARY outcome

Timeframe: Up to approximately 8.5 months

Population: ITT population included all randomized participants.

ORR=percentage of participants with CMR/partial metabolic responses (PMR), based on PET-CT per Lugano response criteria as per an IRC. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at lymph nodes (LN) \& extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum \&/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions \& no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately \> liver; 5=uptake markedly higher than liver \&/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN \& extra lymphatic sites; no new lesions \& residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment	52.7 percentage of participants Interval 43.74 to 61.56	24.6 percentage of participants Interval 17.37 to 33.07	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.

BOR was defined as the best response while on study (based on PET-CT or CT data) according to Lugano response criteria, as determined by the investigator. CMR and PMR based on PET-CT data were defined as outlined in the ORR outcome measure (OM) number 8. CT-based complete radiologic response was defined as target lymphatic nodes/nodal masses regression to ≤ 1.5 centimeters (cm) in longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; absence of non-measured lesion; enlarged organs regress to normal; no new lesions and bone marrow normal by morphology, if indeterminate, immunohistochemistry (IHC) negative. CT-based partial response was defined as ≥50% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) of up to 6 target measurable nodes and extra nodal sites; absent/normal, regressed, but no increase in non-measured lesions; spleen regressed by \>50% in length beyond normal and no new lesions. Percentages are rounded off.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=126 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator	34.9 percentage of participants Interval 26.65 to 43.92	46.7 percentage of participants Interval 21.27 to 73.41	65.1 percentage of participants Interval 56.23 to 73.29

SECONDARY outcome

Timeframe: Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months

Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.

CRR was defined as the percentage of participants who had CMR based positron emission tomography-computed tomography (PET-CT) according to Lugano response criteria at the end of treatment as determined by investigator. CMR was defined as score 1, 2, or 3 (1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \>mediastinum but ≤ liver) with or without a residual mass on 5PS at lymph nodes and extra lymphatic sites. In Waldeyer's ring or extranodal sites with high physiologic uptake or with activation within spleen or marrow (e.g., with chemotherapy/myeloid colony-stimulating factors), uptake may be greater than normal mediastinum and/or liver. In this circumstance, CMR was inferred if uptake at sites of initial involvement is no greater than surrounding normal tissue even if the tissue has high physiologic uptake; no new lesions and no evidence of FDG-avid disease in bone marrow. Percentages are rounded off.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=126 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment	18.3 percentage of participants Interval 11.94 to 26.12	20.0 percentage of participants Interval 4.33 to 48.09	35.7 percentage of participants Interval 27.42 to 44.57

SECONDARY outcome

Timeframe: Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months

Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.

ORR=percentage of participants with CMR/PMR, based on PET-CT as determined by investigator per Lugano response criteria. CMR=score 1, 2, or 3 with/ without a residual mass on 5PS at LN \& extra lymphatic sites. In Waldeyer's ring or extra nodal sites with high physiologic uptake or with activation within spleen/marrow, uptake may be greater than normal mediastinum \&/or liver. In this case, CMR was inferred if uptake at sites of initial involvement was no greater than surrounding normal tissue even if the tissue had high physiologic uptake; no new lesions \& no evidence of FDG-avid disease in bone marrow. PMR=score 4 or 5 on 5PS (4=uptake moderately \> liver; 5=uptake markedly higher than liver \&/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size at LN \& extra lymphatic sites; no new lesions \& residual uptake higher than uptake in normal marrow but reduced compared with baseline. Percentages are rounded off.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=126 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment	24.6 percentage of participants Interval 17.37 to 33.07	26.7 percentage of participants Interval 7.79 to 55.1	45.0 percentage of participants Interval 36.2 to 53.96

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: DOR-evaluable population included all participants who had an objective response (CR or PR).

DOR=time from the date of the first occurrence of a documented objective response (complete or partial response \[CR/PR\]) (based on PET-CT or CT data) as determined by the investigator, using Lugano response criteria, until PD (based on either response: including PET-CT data or not including any PET data) or death, whichever occurred first. CMR and PMR based on PET-CT data were defined as outlined in the ORR OM. CT-based complete and partial response were defined as outlined in the BOR OM. PD defined as outlined in the PFS OM.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=84 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=44 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Duration of Response (DOR)	11.8 months Interval 8.6 to 15.5	8.5 months Interval 3.7 to 26.9	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: Safety run-in population included all participants who received any amount of any study drug during stage 1. ITT population included all randomized participants in stage 2.

EFSeff was defined as the time from randomization to first to the earliest occurrence of the following: PD or relapse using Lugano response criteria (based on either response: including PET-CT data or not including any PET data); death due to any cause or initiation of any NALT. PD based on PET-CT data was defined as score 4 or 5 on 5PS with an increase in intensity of uptake from baseline at individual target nodes/nodal masses and/or new FDG-avid foci extranodal lesions consistent with lymphoma at interim or end-of-treatment assessment. New lesions: New FDG-avid foci consistent with lymphoma rather than another etiology, Bone marrow: New or recurrent FDG-avid foci. Participants with no EFSeff events were censored at the time of the last evaluable tumor assessment if post-baseline assessments were available and participants who did not undergo a post-baseline tumor assessment were censored at the time of randomization. KM method was used to estimate median EFS for each treatment arm.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=126 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: Event-free Survival (EFSeff)	2.7 months Interval 2.5 to 3.3	3.9 months Interval 3.2 to 6.3	6.8 months Interval 5.9 to 9.3

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: ITT population included all randomized participants.

Time to deterioration was defined as the time from randomization to the first documentation of a 10-point decrease in EORTC QLQ-C30 physical functioning scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health status and quality of life (GHS/QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning). KM method was used to estimate median time to deterioration for each treatment arm.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Time to Deterioration in Physical Functioning as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30)	8.1 months Interval 4.2 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	2.8 months Interval 1.4 to 3.0	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: ITT population included all randomized participants.

Time to deterioration was defined as the time from randomization to the first documentation of a 10-point increase from baseline in EORTC QLQ-C30 fatigue scale. EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) was scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). KM method was used to estimate median time to deterioration for each treatment arm.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Time to Deterioration in Fatigue Scale as Measured by the EORTC QLQ-C30	1.8 months Interval 1.5 to 2.8	1.4 months Interval 1.2 to 2.8	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: ITT population included all randomized participants.

Time to deterioration was defined as the time from randomization to the first documentation of a \>3-point decrease from baseline in FACT-Lym LymS. The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0="Not at all" and 4="very much". Scale score range is from 0 to 60. Higher score indicates better quality of life. KM method was used to estimate the median time to deterioration for each treatment arm.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Subscale (FACT-Lym LymS)	4.6 months Interval 2.9 to 7.9	2.5 months Interval 1.4 to 3.2	—

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)

Population: ITT population included all randomized participants. Number analyzed is the number of participants with data available for analysis at the specified timepoint. Participants may have been lost to follow-up/did not complete the specified visit during the study.

EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The functioning items were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher physical functioning).

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Baseline	71.08 score on a scale Standard Deviation 25.09	65.65 score on a scale Standard Deviation 22.83	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Cycle 2 Day 1	0.94 score on a scale Standard Deviation 16.74	-0.88 score on a scale Standard Deviation 16.60	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Cycle 3 Day 1	2.16 score on a scale Standard Deviation 19.57	-1.10 score on a scale Standard Deviation 19.81	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Cycle 5 Day 1	2.68 score on a scale Standard Deviation 20.65	1.28 score on a scale Standard Deviation 17.00	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Cycle 7 Day 1	0.87 score on a scale Standard Deviation 20.39	-1.76 score on a scale Standard Deviation 18.37	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at End of Treatment	-3.70 score on a scale Standard Deviation 22.56	-4.65 score on a scale Standard Deviation 19.00	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 01	-0.80 score on a scale Standard Deviation 20.10	0.91 score on a scale Standard Deviation 19.66	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 02	2.28 score on a scale Standard Deviation 20.11	10.53 score on a scale Standard Deviation 17.54	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 03	0.17 score on a scale Standard Deviation 18.51	4.29 score on a scale Standard Deviation 19.50	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 04	0.65 score on a scale Standard Deviation 14.54	6.67 score on a scale Standard Deviation 15.87	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 05	-2.53 score on a scale Standard Deviation 18.89	7.88 score on a scale Standard Deviation 19.28	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 06	1.54 score on a scale Standard Deviation 16.79	10.00 score on a scale Standard Deviation 15.48	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 07	6.67 score on a scale Standard Deviation 17.95	9.17 score on a scale Standard Deviation 17.43	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 08	5.45 score on a scale Standard Deviation 16.01	14.44 score on a scale Standard Deviation 21.26	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 09	8.48 score on a scale Standard Deviation 19.57	16.67 score on a scale Standard Deviation 17.26	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 10	5.33 score on a scale Standard Deviation 19.66	18.67 score on a scale Standard Deviation 18.50	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 11	11.67 score on a scale Standard Deviation 15.75	5.00 score on a scale Standard Deviation 11.39	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 12	16.67 score on a scale Standard Deviation 23.57	13.33 score on a scale Standard Deviation 11.55	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 13	16.67 score on a scale Standard Deviation 23.57	6.67 score on a scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—
Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 14	33.33 score on a scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—	—

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)

Population: ITT population included all randomized participants. Number analyzed is the number of participants with data available for analysis at the specified time point. Participants may have been lost to follow-up/did not complete the specified visit during the study.

EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom scale (fatigue) were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). A positive change from baseline indicates an improvement.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Baseline	35.13 score on a scale Standard Deviation 28.01	34.99 score on a scale Standard Deviation 25.00	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Cycle 2 Day 1	2.57 score on a scale Standard Deviation 20.30	2.81 score on a scale Standard Deviation 25.16	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Cycle 3 Day 1	0.05 score on a scale Standard Deviation 24.39	2.04 score on a scale Standard Deviation 23.08	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Cycle 5 Day 1	-0.45 score on a scale Standard Deviation 24.88	4.26 score on a scale Standard Deviation 25.44	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Cycle 7 Day 1	0.48 score on a scale Standard Deviation 27.38	4.90 score on a scale Standard Deviation 17.56	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at End of Treatment	6.99 score on a scale Standard Deviation 28.87	7.43 score on a scale Standard Deviation 26.70	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 01	-0.67 score on a scale Standard Deviation 23.37	3.03 score on a scale Standard Deviation 18.84	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 02	-4.97 score on a scale Standard Deviation 19.96	-8.77 score on a scale Standard Deviation 15.96	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 03	-6.27 score on a scale Standard Deviation 18.52	1.59 score on a scale Standard Deviation 24.60	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 04	-9.68 score on a scale Standard Deviation 18.97	-1.71 score on a scale Standard Deviation 17.48	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 05	-7.66 score on a scale Standard Deviation 21.23	0.00 score on a scale Standard Deviation 24.34	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 06	-7.26 score on a scale Standard Deviation 12.94	0.00 score on a scale Standard Deviation 25.66	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 07	-8.50 score on a scale Standard Deviation 16.91	8.33 score on a scale Standard Deviation 17.57	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 08	-10.10 score on a scale Standard Deviation 12.62	0.00 score on a scale Standard Deviation 17.21	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 09	-12.12 score on a scale Standard Deviation 16.82	0.00 score on a scale Standard Deviation 23.31	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 10	-2.22 score on a scale Standard Deviation 4.97	8.89 score on a scale Standard Deviation 19.88	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 11	-8.33 score on a scale Standard Deviation 16.67	11.11 score on a scale Standard Deviation 12.83	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 12	-11.11 score on a scale Standard Deviation 15.71	0.00 score on a scale Standard Deviation 19.24	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 13	-11.11 score on a scale Standard Deviation 15.71	22.22 score on a scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—
Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30 Change at Long-term Follow-up 14	-22.22 score on a scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—	—

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)

Population: ITT population included all randomized participants. Number analyzed is the number of participants with data available for analysis at the specified time point. Participants may have been lost to follow-up/did not complete the specified visit during the study.

The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0="Not at all" and 4="very much". Scale score range is from 0 to 60. Higher score indicates better quality of life. A positive change from baseline indicates an improvement.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Baseline	42.49 score on a scale Standard Deviation 10.94	41.73 score on a scale Standard Deviation 10.88	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Cycle 2 Day 1	2.12 score on a scale Standard Deviation 8.38	0.49 score on a scale Standard Deviation 9.37	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Cycle 3 Day 1	2.66 score on a scale Standard Deviation 9.22	1.71 score on a scale Standard Deviation 8.17	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Cycle 5 Day 1	3.53 score on a scale Standard Deviation 8.10	1.95 score on a scale Standard Deviation 8.15	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Cycle 7 Day 1	2.69 score on a scale Standard Deviation 10.45	0.32 score on a scale Standard Deviation 8.23	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at End of Treatment	2.34 score on a scale Standard Deviation 11.09	-0.71 score on a scale Standard Deviation 10.34	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 01	2.88 score on a scale Standard Deviation 10.03	0.14 score on a scale Standard Deviation 13.10	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 02	5.32 score on a scale Standard Deviation 8.15	5.22 score on a scale Standard Deviation 9.28	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 03	3.90 score on a scale Standard Deviation 7.32	4.08 score on a scale Standard Deviation 7.31	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 04	4.29 score on a scale Standard Deviation 6.47	6.00 score on a scale Standard Deviation 6.18	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 05	4.07 score on a scale Standard Deviation 6.87	6.00 score on a scale Standard Deviation 9.56	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 06	4.15 score on a scale Standard Deviation 6.16	5.89 score on a scale Standard Deviation 6.75	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 07	4.65 score on a scale Standard Deviation 7.56	5.29 score on a scale Standard Deviation 7.54	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 08	5.82 score on a scale Standard Deviation 5.46	8.00 score on a scale Standard Deviation 4.53	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 09	7.82 score on a scale Standard Deviation 6.63	8.80 score on a scale Standard Deviation 5.81	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 10	4.00 score on a scale Standard Deviation 3.32	7.50 score on a scale Standard Deviation 7.23	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 11	6.75 score on a scale Standard Deviation 5.44	5.67 score on a scale Standard Deviation 7.02	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 12	4.50 score on a scale Standard Deviation 4.95	5.50 score on a scale Standard Deviation 0.71	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 13	4.00 score on a scale Standard Deviation 4.24	13.00 score on a scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—
Stage 2: Change From Baseline in FACT-Lym LYMS Scores Change at Long-term Follow-up 14	8.00 score on a scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—	—

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7 and 8 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months)

Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints. Participants may have been lost to follow-up/did not complete the specified visit during the study.

The FACT/GOG-NTX scale provides a targeted assessment of symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. It contains 12 items scored from 0-4, where 0="Not at all" and 4="very much". Scores are summed for a range of 12-44, with lower scores indicating more severe neurotoxicity. Participants completed assessments until progression or non-protocol-specified anti-lymphoma treatment (NALT). Only records on or before the first NALT were summarized.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=128 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=125 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 11	-1.50 score on scale Standard Deviation 1.91	-1.50 score on scale Standard Deviation 4.80	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 12	-1.50 score on scale Standard Deviation 0.71	-0.33 score on scale Standard Deviation 4.16	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 13	-2.00 score on scale Standard Deviation 0.00	-5.00 score on scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 14	39.00 score on scale Standard Deviation NA The standard deviation was not estimable for a single participant.	—	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 10	-4.60 score on scale Standard Deviation 6.02	1.20 score on scale Standard Deviation 7.40	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Cycle 7 Day 1	-4.25 score on scale Standard Deviation 9.97	-2.00 score on scale Standard Deviation 4.77	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Cycle 8 Day 1	-5.08 score on scale Standard Deviation 10.41	-3.62 score on scale Standard Deviation 4.95	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at End of Treatment	-5.96 score on scale Standard Deviation 11.05	-3.80 score on scale Standard Deviation 7.65	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 01	-9.50 score on scale Standard Deviation 11.00	-4.91 score on scale Standard Deviation 9.11	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 02	-6.86 score on scale Standard Deviation 7.75	-3.77 score on scale Standard Deviation 7.00	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Baseline	40.37 score on scale Standard Deviation 8.32	40.67 score on scale Standard Deviation 6.70	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Cycle 2 Day 1	-0.54 score on scale Standard Deviation 6.87	-1.56 score on scale Standard Deviation 5.60	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Cycle 3 Day 1	-0.20 score on scale Standard Deviation 8.01	-1.35 score on scale Standard Deviation 4.91	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Cycle 4 Day 1	-0.78 score on scale Standard Deviation 7.58	-2.44 score on scale Standard Deviation 6.82	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Cycle 5 Day 1	-1.68 score on scale Standard Deviation 7.95	-2.35 score on scale Standard Deviation 4.54	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Cycle 6 Day 1	-3.48 score on scale Standard Deviation 8.92	-2.02 score on scale Standard Deviation 5.47	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 03	-7.73 score on scale Standard Deviation 7.04	-4.73 score on scale Standard Deviation 7.22	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 04	-5.18 score on scale Standard Deviation 5.96	-0.85 score on scale Standard Deviation 6.35	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 05	-4.92 score on scale Standard Deviation 5.85	-1.55 score on scale Standard Deviation 3.91	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 06	-4.58 score on scale Standard Deviation 6.79	-1.20 score on scale Standard Deviation 5.22	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 07	-3.62 score on scale Standard Deviation 6.18	-3.00 score on scale Standard Deviation 6.55	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 08	-3.05 score on scale Standard Deviation 7.02	0.83 score on scale Standard Deviation 5.71	—
Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores Change at Long-term Follow-up 09	-4.20 score on scale Standard Deviation 4.42	0.83 score on scale Standard Deviation 5.56	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: ITT population included all randomized participants in Stage 2.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Physical Functioning Scale	41.1 percentage of participants Interval 32.5 to 50.09	31.0 percentage of participants Interval 23.02 to 39.8	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: ITT population included all randomized participants in Stage 2.

EORTC QLQ-C30 consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The symptom items were scored on a 4-point scale that ranged from "not at all" to "very much". Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher symptom severity). Clinically meaningful improvement was defined as a participant with at least a 9 point scale score decrease.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Fatigue Scale	55.8 percentage of participants Interval 46.81 to 64.55	46.0 percentage of participants Interval 37.12 to 55.14	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: ITT population included all randomized participants in Stage 2.

The FACT-Lym subscale has 4 domains: physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma-specific subscale (LymS). The FACT-Lym LYMS consists of common lymphoma disease and/or treatment-related symptoms (e.g., pain, fever, swelling, night sweats, insomnia, itching, weight loss, fatigue, and loss of appetite). FACT-Lym LYMS contains 15 items scored from 0-4, where 0="Not at all" and 4="very much". Scale score range is from 0 to 60. Higher score indicates better quality of life. Clinically meaningful improvement was defined as a 3-point increase from baseline.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=129 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=126 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Percentage of Participants With Clinically Meaningful Improvement in FACT-Lym LYMS	66.7 percentage of participants Interval 57.83 to 74.72	48.4 percentage of participants Interval 39.42 to 57.48	—

SECONDARY outcome

Timeframe: From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months)

Population: Safety-evaluable population included all participants who received any amount of any study drug (regardless of the stage).

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=128 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=125 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Number of Participants With AEs	125 Participants	117 Participants	—

SECONDARY outcome

Timeframe: From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months)

Population: Safety-evaluable population included all participants who received any amount of any study drug (regardless of the stage).

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=128 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=125 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 2: Number of Participants With PN	73 Participants	36 Participants	—

SECONDARY outcome

Timeframe: Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months

Population: Safety population included all participants who received any amount of any study drug (regardless of the stage).

Dose modifications (interruptions/reductions) were based on physical examination findings, observed toxicities, and laboratory results obtained within 72 hours before study treatment administration. The determination of all dose modifications was made based on the investigator's assessment of ongoing clinical benefit with continuing study treatment. Dosing occurred only when a participant's clinical assessment and laboratory test values were acceptable.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=128 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: Number of Participants With Dose Modification for Polatuzumab Vedotin	22 Participants	3 Participants	—

SECONDARY outcome

Timeframe: Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months

Population: Safety population included all participants who received any amount of any study drug (regardless of the stage).

Dose intensity = (total dose actually received divided by the expected total dose)\*100. Expected total dose for dose intensity accounting for delay/reduction is based on the expected number of cycles between the first and last exposure of each drug. Percentage of dose intensity accounting for delay/reduction in dose by the participants in each arm is reported here.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=128 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: Dose Intensity of Polatuzumab Vedotin	92.81 percentage of dose Standard Deviation 10.33	93.60 percentage of dose Standard Deviation 11.23	—

SECONDARY outcome

Timeframe: From randomization to the death (up to approximately 34 months)

Population: Safety run-in population included all participants who received any amount of any study drug during safety run-in stage.

OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. KM method was used to estimate median OS for each treatment arm.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=15 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1: OS	—	12.6 months Interval 11.4 to The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.	—

SECONDARY outcome

Timeframe: Up to approximately 34 months

Population: Immunogenicity-evaluable population included all participants who received at least one dose of polatuzumab vedotin with at least one evaluable post-baseline ADA sample.

Treatment emergent ADA-positive participants after drug administration were determined for participants exposed to polatuzumab vedotin. Participants positive for treatment emergent ADA were defined as the number of post-baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = a participant with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Percentages are rounded off.

Outcome measures

Outcome measures
Measure	Stage 2: Pola-R-GemOx n=117 Participants Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin, 1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: R-GemOx n=12 Participants R-GemOx: Participants received rituximab, 375 mg/m\^2, IV on Day 1, followed by gemcitabine, 1000 mg/m\^2, IV and oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.	Stage 2: Pola-R-GemOx Participants received rituximab, 375 mg/m\^2, IV, followed by polatuzumab vedotin,1.8 mg/kg, IV on Day 1 of each 21-day cycle. Participants also received gemcitabine, 1000 mg/m\^2, IV followed by oxaliplatin 100 mg/m\^2, IV on Day 2 of each 21-day cycle for up to 8 cycles.
Stage 1 and Stage 2: Percentage of Participants With Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin	2.6 percentage of participants	0 percentage of participants	—

Adverse Events

Stage 2: Pola-R-GemOx

Serious events: 49 serious events

Other events: 119 other events

Deaths: 68 deaths

Pola-R-GemOx - Pooled

Serious events: 51 serious events

Other events: 133 other events

Deaths: 77 deaths

Stage 1: Pola-R-GemOx

Serious events: 2 serious events

Other events: 14 other events

Deaths: 9 deaths

Stage 2: R-GemOx

Serious events: 39 serious events

Other events: 111 other events

Deaths: 83 deaths

Serious adverse events

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