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A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

Primary Purpose

Lymphoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Bendamustine

Obinutuzumab

Polatuzumab vedotin (Liquid)

Rituximab

Polatuzumab vedotin (Lyophilized)

About this trial

This is an interventional treatment trial for Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL
If the participant has received prior bendamustine, response duration must have been greater than (>) 1 year (for participants who have relapse disease after a prior regimen)
At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension
Confirmed availability of archival or freshly collected tumor tissue
The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review.
Life expectancy of at least 24 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Adequate hematological function unless inadequate function is due to underlying disease

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, rituximab, or obinutuzumab
Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives 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 per day prednisone or equivalent, for purposes other than lymphoma symptom control
Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1 Day 1
Prior allogeneic SCT
Eligibility for autologous SCT
Grade 3b FL
History of transformation of indolent disease to DLBCL
Primary or secondary CNS lymphoma
Current Grade >1 peripheral neuropathy
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
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 within 4 weeks prior to Cycle 1 Day 1
Suspected or latent tuberculosis
Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C virus (HCV) antibody
Known history of human immunodeficiency virus (HIV) seropositive status or known infection with human T-cell leukemia virus 1 (HTLV-1) virus
Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort
Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation function tests
Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle 1, Day 1

Sites / Locations

University of Alabama at Birmingham
Clearview Cancer Institute
City of Hope National Medical Center
Univ of Colorado Canc Ctr
Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
Emory Univ Winship Cancer Inst
Joliet Oncology-Hematology; Associates, Ltd.
Horizon Oncology Research, Inc.
Weinberg CA Inst Franklin Sq
Regional Cancer Care Associates LLC - Morristown
University of New Mexico Cancer Center
Memorial Sloan Kettering Cancer Center
Levine Cancer Institute
West Clinic
Swedish Cancer Inst.
Northwest Medical Specialties
Prince of Wales Hospital; Oncology
Royal Adelaide Hospital
Adelaide Cancer Centre
Monash Medical Centre; Haematology Research
BCCA-Vancouver Cancer Centre
Queen Elizabeth II Health Sciences Centre; Oncology
Hopital Maisonneuve- Rosemont; Oncology
Jewish General Hospital
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
Fakultni nemocnice Hradec Kralove
Fakultní nemocnice Ostrava Klinika hematoonkologie
I Interni klinika; Vseobecna fakultni nemocnice
Chu Site Du Bocage;Hematologie Clinique
Centre Hospitalier Departemental Les Oudairies
Centre Leon Berard; Departement Oncologie Medicale
CHU Saint Eloi; Service d'Hématologie Clinique
CHU Lyon Sud - Service Hématologie
Centre Henri Becquerel; Hematologie
HELIOS Klinikum Erfurt - Innere Medizin - 4. Medizinische Klinik, Hämatologie
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Abt. für Hämatologie und Onkologie
Joh. Wesling Klinikum Minden; Klinik fuer Hämatologie und Onkologie
Gemeinschaftspraxis für Hämatologie und Onkologie
Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale
Semmelweis University, First Dept of Medicine
National Institute of Oncology, A Dept of Internal Medicine
University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B
Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia
Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
Seoul National University Hospital
Samsung Medical Center
UMC St. Radboud; Hematology
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
Hospital Clinic i Provincial de Barcelona; Hematology
Hospital Universitario la Paz; Servicio de Hematologia
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
Ankara University; Hematology
Dokuz Eylul Uni ; Hematology
Ondokuzmayis University Medical Faculty Heamatology Department
Karadeniz Technical Uni School of Medicine; Hematology
KINGS COLLEGE HOSPITAL; Commercial R&D Amendments, Kings Health Partners Clinical Trials Office
Christie Hospital Nhs Trust; Medical Oncology
Nottingham City Hospital; Dept of Haematology
Southampton General Hospital; Somers Cancer Research Building

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

Arm A (Phase II Randomization): Polatuzumab+BR in FL

Arm B (Phase II Randomization): BR in FL

Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL

Arm D (Phase II Randomization): BR in DLBCL

Arm E (Phase II Expansion): Polatuzumab+BG in FL

Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL

Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL

Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL

Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL

Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL

Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL

Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL

Arm Description

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.

Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.

Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.

In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.

In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.

Outcomes

Primary Outcome Measures

Phase Ib: Percentage of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).

Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin

The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = 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. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)

The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = 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. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)

CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) 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 evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS 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 evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)

Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms*day per milliliters.

Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)

Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Secondary Outcome Measures

Phase II: Percentage of Participants With AEs

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin

The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = 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. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator

CR was assessed by investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS 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 evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS 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 evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT complete MR in lymph nodes and ELS 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, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS 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. Bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator

CR was determined by investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimetres (cm) in in longest transverse diameter (LDi) and no ELS of disease 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 for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC

CR was determined by IRC a at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease 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 for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).

Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).

Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator

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

DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC

DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator

DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT>UT in normal bone marrow but<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.

DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC

DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver &/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL & residual mass of any size at interim for LN & ELS;residual UT>UT in normal bone marrow but<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN & ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.

DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator

PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC

PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator

CR was assessed by Investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS 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 evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS 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, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS 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, bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator

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

Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator

PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC

PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator

EFS was defined as time from randomization to disease progression or relapse, as assessed by the investigator or death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.

Phase II NF Cohorts: Overall Survival (OS)

OS was defined as the time from the date of randomization or first treatment (for obinutuzumab arms) to the date of death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS 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 evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator

CR was determined by Investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease 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 for DLBCL cohorts). Values have been rounded off to the nearest whole number.

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC

CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease 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 for DLBCL cohorts). Values have been rounded off to the nearest whole number.

Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).

Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).

Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE

PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE

PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab

PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab

PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Plasma Concentration of Bendamustine

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H).

Serum Concentration of Rituximab

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H).

Serum Concentration of Obinutuzumab

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody and unconjugated MMAE were measured.

Phase II: Cmax of Bendamustine and Rituximab in Arms B and D

Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F

PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured.

Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day*micrograms per milliliter [day*ug/mL]).

Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured.

Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase II: CL of Bendamustine and Rituximab in Arms B and D

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Phase II: Vss of Bendamustine and Rituximab in Arms B and D

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F

The TINAS is an 11-item questionnaire that assesses the severity of neuropathy-related symptoms in the last 24 hours. The 11 items assessed were: hot/burning sensations in hands/feet, sensations pins and needles arms/legs, numbness or tingling in hands/feet, sensations of electric shock, pain when touching cold things, cramps in hands/feet, discomfort when touching things, discomfort skin contact with something, trouble grasping small objects, trouble walking loss feeling legs/feet, difficulty balance loss feeling leg/feet. Each item was scored on a 0-10 scale, with 0 being the symptom is not present, and 10 being the symptom is as bad as the participant can imagine. Higher scores indicate more severe disease. Scores were averaged at each week.

Full Information

NCT ID

NCT02257567

First Posted

October 2, 2014

Last Updated

October 18, 2022

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT02257567

Brief Title

A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

Official Title

A Phase IB/II Study Evaluating The Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination With Rituximab (R) or Obinutuzumab (G) Plus Bendamustine (B) in Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

October 15, 2014 (Actual)

Primary Completion Date

October 21, 2021 (Actual)

Study Completion Date

October 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

331 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A (Phase II Randomization): Polatuzumab+BR in FL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.

Arm Title

Arm B (Phase II Randomization): BR in FL

Arm Type

Active Comparator

Arm Description

Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.

Arm Title

Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.

Arm Title

Arm D (Phase II Randomization): BR in DLBCL

Arm Type

Active Comparator

Arm Description

Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.

Arm Title

Arm E (Phase II Expansion): Polatuzumab+BG in FL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.

Arm Title

Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.

Arm Title

Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.

Arm Title

Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.

Arm Title

Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.

Arm Title

Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL

Arm Type

Experimental

Arm Description

Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.

Arm Title

Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL

Arm Type

Experimental

Arm Description

In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.

Arm Title

Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL

Arm Type

Experimental

Arm Description

In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.

Intervention Type

Drug

Intervention Name(s)

Bendamustine

Other Intervention Name(s)

Treanda; Ribomustin; Levact

Intervention Description

Bendamustine 90 milligrams per meter-squared (mg/m^2) per day administered IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Intervention Type

Drug

Intervention Name(s)

Obinutuzumab

Other Intervention Name(s)

GA101; Gazyva; Gazyvaro

Intervention Description

Obinutuzumab 1000 milligrams (mg) IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Intervention Type

Drug

Intervention Name(s)

Polatuzumab vedotin (Liquid)

Other Intervention Name(s)

DCDS4501A

Intervention Description

Polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) administered IV on Day 2 of Cycle 1, then on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Rituxan; MabThera

Intervention Description

Rituximab standard dose, 375 mg/m^2 IV on Day 1 of each cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).

Intervention Type

Drug

Intervention Name(s)

Polatuzumab vedotin (Lyophilized)

Other Intervention Name(s)

DCDS4501S

Intervention Description

Participants in the New Formulation (NF) Cohort (Arms G and H) will follow the same schedule and dosing requirements as participants in the other Phase II cohorts (Arms A-F).

Primary Outcome Measure Information:

Title

Phase Ib: Percentage of Participants With Adverse Events (AEs)

Description

Time Frame

From the study start up to the end of the study (up to approximately 84 months)

Title

Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs

Description

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Time Frame

From Month 37 to Month 84 (up to approximately 47 months)

Title

Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin

Description

Time Frame

Baseline up to approximately Month 24

Title

Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Description

Time Frame

Baseline up to approximately Month 24

Title

Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)

Description

Time Frame

From Month 37 to Month 84 (up to approximately 47 months)

Title

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

Description

Time Frame

6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Title

Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)

Description

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks

Title

Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Title

Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Title

Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Secondary Outcome Measure Information:

Title

Phase II: Percentage of Participants With AEs

Description

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.

Time Frame

From the study start up to the end of the study (up to approximately 84 months)

Title

Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin

Description

The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = 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. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.

Time Frame

Baseline to approximately Month 24

Title

Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab

Description

Time Frame

Baseline to approximately Month 24

Title

Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

Description

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS 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 evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)

Title

Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator

Description

Time Frame

Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)

Title

DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC

Description

Time Frame

Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)

Title

DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator

Description

Time Frame

From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)

Title

DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC

Description

Time Frame

From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)

Title

DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator

Description

Time Frame

From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)

Title

DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC

Description

PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Time Frame

From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)

Title

Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Title

Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Title

Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC

Description

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS 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, bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Title

Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator

Description

Time Frame

Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])

Title

Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC

Description

Time Frame

Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])

Title

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator

Description

Time Frame

From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])

Title

Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC

Description

Time Frame

Title

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator

Description

Time Frame

From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])

Title

Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC

Description

PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.

Time Frame

From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])

Title

Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator

Description

Time Frame

From Month 37 to Month 84 (up to approximately 47 months)

Title

Phase II NF Cohorts: Overall Survival (OS)

Description

Time Frame

From Month 37 to Month 84 (up to approximately 47 months)

Title

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC

Description

CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS 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 evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Title

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Title

Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC

Description

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)

Title

Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator

Description

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)

Title

Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC

Description

OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).

Time Frame

6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)

Title

Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE

Description

PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time Frame

Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Title

Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE

Description

PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Time Frame

Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose

Title

Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab

Description

PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time Frame

Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)

Title

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab

Description

PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Time Frame

Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose

Title

Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

Description

PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time Frame

Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Title

Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE

Description

PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.

Time Frame

Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose

Title

Plasma Concentration of Bendamustine

Description

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H).

Time Frame

Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose

Title

Serum Concentration of Rituximab

Description

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H).

Time Frame

Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)

Title

Serum Concentration of Obinutuzumab

Description

Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.

Time Frame

Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)

Title

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

Description

PK of three pola-related analytes: acMMAE, total antibody and unconjugated MMAE were measured.

Time Frame

Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: Cmax of Bendamustine and Rituximab in Arms B and D

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F

Description

PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured.

Time Frame

Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Title

Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day*micrograms per milliliter [day*ug/mL]).

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)

Description

PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks

Title

Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: CL of Bendamustine and Rituximab in Arms B and D

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Title

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: Vss of Bendamustine and Rituximab in Arms B and D

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)

Title

Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)

Description

PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.

Time Frame

Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks

Title

Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F

Description

Time Frame

Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL If the participant has received prior bendamustine, response duration must have been greater than (>) 1 year (for participants who have relapse disease after a prior regimen) At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension Confirmed availability of archival or freshly collected tumor tissue The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review. Life expectancy of at least 24 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Adequate hematological function unless inadequate function is due to underlying disease 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, rituximab, or obinutuzumab Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives 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 per day prednisone or equivalent, for purposes other than lymphoma symptom control Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1 Day 1 Prior allogeneic SCT Eligibility for autologous SCT Grade 3b FL History of transformation of indolent disease to DLBCL Primary or secondary CNS lymphoma Current Grade >1 peripheral neuropathy Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm) 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 within 4 weeks prior to Cycle 1 Day 1 Suspected or latent tuberculosis Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C virus (HCV) antibody Known history of human immunodeficiency virus (HIV) seropositive status or known infection with human T-cell leukemia virus 1 (HTLV-1) virus Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation function tests Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle 1, Day 1

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294-3300

Country

United States

Facility Name

Clearview Cancer Institute

City

Huntsville

State/Province

Alabama

ZIP/Postal Code

35805

Country

United States

Facility Name

City of Hope National Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Univ of Colorado Canc Ctr

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32256

Country

United States

Facility Name

Emory Univ Winship Cancer Inst

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Joliet Oncology-Hematology; Associates, Ltd.

City

Joliet

State/Province

Illinois

ZIP/Postal Code

60435

Country

United States

Facility Name

Horizon Oncology Research, Inc.

City

Lafayette

State/Province

Indiana

ZIP/Postal Code

47905

Country

United States

Facility Name

Weinberg CA Inst Franklin Sq

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21237

Country

United States

Facility Name

Regional Cancer Care Associates LLC - Morristown

City

Morristown

State/Province

New Jersey

ZIP/Postal Code

07962

Country

United States

Facility Name

University of New Mexico Cancer Center

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87131

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Levine Cancer Institute

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

West Clinic

City

Germantown

State/Province

Tennessee

ZIP/Postal Code

38138

Country

United States

Facility Name

Swedish Cancer Inst.

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

Facility Name

Northwest Medical Specialties

City

Tacoma

State/Province

Washington

ZIP/Postal Code

98405

Country

United States

Facility Name

Prince of Wales Hospital; Oncology

City

Randwick

State/Province

New South Wales

ZIP/Postal Code

2031

Country

Australia

Facility Name

Royal Adelaide Hospital

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

Facility Name

Adelaide Cancer Centre

City

Kurralta Park

State/Province

South Australia

ZIP/Postal Code

5037

Country

Australia

Facility Name

Monash Medical Centre; Haematology Research

City

Clayton

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

Facility Name

BCCA-Vancouver Cancer Centre

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 4E6

Country

Canada

Facility Name

Queen Elizabeth II Health Sciences Centre; Oncology

City

Halifax

State/Province

Nova Scotia

ZIP/Postal Code

B3H 2Y9

Country

Canada

Facility Name

Hopital Maisonneuve- Rosemont; Oncology

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H1T 2M4

Country

Canada

Facility Name

Jewish General Hospital

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3T 1E2

Country

Canada

Facility Name

Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika

City

Brno

ZIP/Postal Code

625 00

Country

Czechia

Facility Name

Fakultni nemocnice Hradec Kralove

City

Hradec Kralove

ZIP/Postal Code

500 05

Country

Czechia

Facility Name

Fakultní nemocnice Ostrava Klinika hematoonkologie

City

Ostrava

ZIP/Postal Code

70852

Country

Czechia

Facility Name

I Interni klinika; Vseobecna fakultni nemocnice

City

Prague 2

ZIP/Postal Code

128 08

Country

Czechia

Facility Name

Chu Site Du Bocage;Hematologie Clinique

City

Dijon

ZIP/Postal Code

21079

Country

France

Facility Name

Centre Hospitalier Departemental Les Oudairies

City

La Roche Sur Yon

ZIP/Postal Code

85925

Country

France

Facility Name

Centre Leon Berard; Departement Oncologie Medicale

City

Lyon

ZIP/Postal Code

69373

Country

France

Facility Name

CHU Saint Eloi; Service d'Hématologie Clinique

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

CHU Lyon Sud - Service Hématologie

City

Pierre Benite

ZIP/Postal Code

69310

Country

France

Facility Name

Centre Henri Becquerel; Hematologie

City

Rouen

ZIP/Postal Code

76038

Country

France

Facility Name

HELIOS Klinikum Erfurt - Innere Medizin - 4. Medizinische Klinik, Hämatologie

City

Erfurt

ZIP/Postal Code

99089

Country

Germany

Facility Name

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Abt. für Hämatologie und Onkologie

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

Joh. Wesling Klinikum Minden; Klinik fuer Hämatologie und Onkologie

City

Minden

ZIP/Postal Code

32429

Country

Germany

Facility Name

Gemeinschaftspraxis für Hämatologie und Onkologie

City

Münster

ZIP/Postal Code

48153

Country

Germany

Facility Name

Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale

City

Regensburg

ZIP/Postal Code

93053

Country

Germany

Facility Name

Semmelweis University, First Dept of Medicine

City

Budapest

ZIP/Postal Code

1083

Country

Hungary

Facility Name

National Institute of Oncology, A Dept of Internal Medicine

City

Budapest

ZIP/Postal Code

1122

Country

Hungary

Facility Name

University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B

City

Debrecen

ZIP/Postal Code

4032

Country

Hungary

Facility Name

Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica

City

Napoli

State/Province

Campania

ZIP/Postal Code

80131

Country

Italy

Facility Name

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia

City

Brescia

State/Province

Lombardia

ZIP/Postal Code

25123

Country

Italy

Facility Name

Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20141

Country

Italy

Facility Name

Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia

City

Alessandria

State/Province

Piemonte

ZIP/Postal Code

15121

Country

Italy

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Samsung Medical Center

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

UMC St. Radboud; Hematology

City

Nijmegen

ZIP/Postal Code

6525 GA

Country

Netherlands

Facility Name

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Clinic i Provincial de Barcelona; Hematology

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Hospital Universitario la Paz; Servicio de Hematologia

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

Ankara University; Hematology

City

Ankara

ZIP/Postal Code

06620

Country

Turkey

Facility Name

Dokuz Eylul Uni ; Hematology

City

Izmir

ZIP/Postal Code

35100

Country

Turkey

Facility Name

Ondokuzmayis University Medical Faculty Heamatology Department

City

Samsun

ZIP/Postal Code

55139

Country

Turkey

Facility Name

Karadeniz Technical Uni School of Medicine; Hematology

City

Trabzon

ZIP/Postal Code

61800

Country

Turkey

Facility Name

KINGS COLLEGE HOSPITAL; Commercial R&D Amendments, Kings Health Partners Clinical Trials Office

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

Christie Hospital Nhs Trust; Medical Oncology

City

Manchester

ZIP/Postal Code

M2O 4BX

Country

United Kingdom

Facility Name

Nottingham City Hospital; Dept of Haematology

City

Nottingham

ZIP/Postal Code

NG5 1PB

Country

United Kingdom

Facility Name

Southampton General Hospital; Somers Cancer Research Building

City

Southampton

ZIP/Postal Code

SO16 6YD

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35086141

Citation

Herrera AF, Tracy S, Croft B, Opat S, Ray J, Lovejoy AF, Musick L, Paulson JN, Sehn LH, Jiang Y. Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA. Blood Adv. 2022 Mar 22;6(6):1651-1660. doi: 10.1182/bloodadvances.2021006415.

Results Reference

derived

PubMed Identifier

34749395

Citation

Sehn LH, Hertzberg M, Opat S, Herrera AF, Assouline S, Flowers CR, Kim TM, McMillan A, Ozcan M, Safar V, Salles G, Ku G, Hirata J, Chang YM, Musick L, Matasar MJ. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022 Jan 25;6(2):533-543. doi: 10.1182/bloodadvances.2021005794.

Results Reference

derived

PubMed Identifier

33028076

Citation

Betts KA, Thuresson PO, Felizzi F, Du EX, Dieye I, Li J, Schulz M, Masaquel AS. US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma. J Comp Eff Res. 2020 Oct;9(14):1003-1015. doi: 10.2217/cer-2020-0057. Epub 2020 Oct 8. Erratum In: J Comp Eff Res. 2021 Mar;10(4):337.

Results Reference

derived

PubMed Identifier

32770353

Citation

Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.

Results Reference

derived

PubMed Identifier

32705923

Citation

Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.

Results Reference

derived

PubMed Identifier

31693429

Citation

Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.

Results Reference

derived

Learn more about this trial

A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

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