TriangleNCT02257567 · CITED IN SOURCE DOCUMENTS
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
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE1, PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2022-11-14
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.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Phase Ib: Percentage of Participants With Adverse Events (AEs)
Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
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)
Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
Phase II: Percentage of Participants With AEs
Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin
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
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
Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator
Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator
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
DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC
DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator
DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC
Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator
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
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC
Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator
Phase II NF Cohorts: Overall Survival (OS)
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Plasma Concentration of Bendamustine
Serum Concentration of Rituximab
Serum Concentration of Obinutuzumab
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
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
Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)
Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
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
Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
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
Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
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
Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)
Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
- intervention Names
- Drug: Bendamustine
- Drug: Polatuzumab vedotin (Liquid)
- Drug: Rituximab
- label
- Arm A (Phase II Randomization): Polatuzumab+BR in FL
- type
- EXPERIMENTAL
- description
- Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.
- intervention Names
- Drug: Bendamustine
- Drug: Rituximab
- label
- Arm B (Phase II Randomization): BR in FL
- type
- ACTIVE_COMPARATOR
- description
- Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
- intervention Names
- Drug: Bendamustine
- Drug: Polatuzumab vedotin (Liquid)
- Drug: Rituximab
- label
- Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL
- type
- EXPERIMENTAL
- description
- Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.
- intervention Names
- Drug: Bendamustine
- Drug: Rituximab
- label
- Arm D (Phase II Randomization): BR in DLBCL
- type
- ACTIVE_COMPARATOR
- description
- Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
- intervention Names
- Drug: Bendamustine
- Drug: Obinutuzumab
- Drug: Polatuzumab vedotin (Liquid)
- label
- Arm E (Phase II Expansion): Polatuzumab+BG in FL
- type
- EXPERIMENTAL
- description
- Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
- intervention Names
- Drug: Bendamustine
- Drug: Obinutuzumab
- Drug: Polatuzumab vedotin (Liquid)
- label
- Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL
- type
- EXPERIMENTAL
- description
- Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
- intervention Names
- Drug: Bendamustine
- Drug: Polatuzumab vedotin (Liquid)
- Drug: Rituximab
- label
- Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL
- type
- EXPERIMENTAL
- description
- Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
- intervention Names
- Drug: Bendamustine
- Drug: Polatuzumab vedotin (Liquid)
- Drug: Rituximab
- label
- Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL
- type
- EXPERIMENTAL
- description
- Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
- intervention Names
- Drug: Bendamustine
- Drug: Obinutuzumab
- Drug: Polatuzumab vedotin (Liquid)
- label
- Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL
- type
- EXPERIMENTAL
- description
- Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
- intervention Names
- Drug: Bendamustine
- Drug: Obinutuzumab
- Drug: Polatuzumab vedotin (Liquid)
- label
- Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL
- type
- EXPERIMENTAL
- description
- In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
- intervention Names
- Drug: Bendamustine
- Drug: Rituximab
- Drug: Polatuzumab vedotin (Lyophilized)
- label
- Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL
- type
- EXPERIMENTAL
- description
- In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL.
- intervention Names
- Drug: Bendamustine
- Drug: Rituximab
- Drug: Polatuzumab vedotin (Lyophilized)
- label
- Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- 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
- Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL
- Arm H (Phase II NF Cohort): Polatuzumab+BR 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
- 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).
- name
- Bendamustine
- other Names
- Treanda; Ribomustin; Levact
- type
- DRUG
- arm Group Labels
- Arm E (Phase II Expansion): Polatuzumab+BG in FL
- Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL
- Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL
- Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL
- 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).
- name
- Obinutuzumab
- other Names
- GA101; Gazyva; Gazyvaro
- type
- DRUG
- arm Group Labels
- Arm A (Phase II Randomization): Polatuzumab+BR in FL
- Arm C (Phase II Randomization): Polatuzumab+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
- 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).
- name
- Polatuzumab vedotin (Liquid)
- other Names
- DCDS4501A
- type
- DRUG
- arm Group Labels
- 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 G (Phase II NF Cohort): Polatuzumab+BR in DLBCL
- Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL
- Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL
- Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL
- 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).
- name
- Rituximab
- other Names
- Rituxan; MabThera
- type
- DRUG
- arm Group Labels
- Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL
- Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL
- 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).
- name
- Polatuzumab vedotin (Lyophilized)
- other Names
- DCDS4501S
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 331
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- 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 adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
- measure
- Phase Ib: Percentage of Participants With Adverse Events (AEs)
- time Frame
- From the study start up to the end of the study (up to approximately 84 months)
- 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.
- measure
- Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
- time Frame
- From Month 37 to Month 84 (up to approximately 47 months)
- 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 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.
- measure
- Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
- time Frame
- Baseline up to approximately Month 24
- description
- 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.
- measure
- Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
- time Frame
- Baseline up to approximately Month 24
- description
- 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.
- measure
- Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
- time Frame
- From Month 37 to Month 84 (up to approximately 47 months)
- description
- 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.
- measure
- 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)
- 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)
- 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) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
- measure
- Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
- 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)
- description
- 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.
- measure
- Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
- 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
- description
- PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
- measure
- Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
- 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
- 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)
- measure
- Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
- 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
- description
- PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
- measure
- Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
- 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 Outcomes
- 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.
- measure
- Phase II: Percentage of Participants With AEs
- time Frame
- From the study start up to the end of the study (up to approximately 84 months)
- 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.
- measure
- Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin
- time Frame
- Baseline to approximately Month 24
- description
- 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.
- measure
- Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
- time Frame
- Baseline to approximately Month 24
- description
- 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.
- measure
- Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
- 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)
- 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.
- measure
- 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
- 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)
- description
- 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).
- measure
- Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator
- 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)
- 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).
- measure
- Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
- 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)
- description
- 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.
- measure
- Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
- 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)
- description
- 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.
- measure
- Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
- 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)
- 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; 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).
- measure
- Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
- 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)
- 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; 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).
- measure
- Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
- 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)
- description
- 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.
- measure
- Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator
- time Frame
- Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
Full 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.
Source references
- references
- citation
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- 38843483
- type
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- 37981564
- type
- DERIVED
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- 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.
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- 35086141
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- 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.
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- 33028076
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- pmid
- 32770353
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- 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.
- pmid
- 32705923
- type
- DERIVED
- 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.
- pmid
- 31693429
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice