Phase 2
Completed N=331
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
Source: ClinicalTrials.gov NCT02257567 ↗Enrolled (actual)
331
Serious AEs
55.4%
Results posted
Nov 2022
Primary outcomePrimary: Phase Ib: Percentage of Participants With Adverse Events (AEs) — 100; 100; 100; 100 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase Ib: Percentage of Participants With Adverse Events (AEs) |
100; 100; 100; 100 | — |
| PRIMARY Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs |
99.1 | — |
| PRIMARY Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin |
50.0; 33.3; 0; 33.3 | — |
| PRIMARY Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized) |
0.0; 1.6; 2.6; 5.0 | — |
| PRIMARY 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) |
69.2; 63.4; 42.5; 17.5; 39.6 | 0.5353 |
| PRIMARY Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC |
42.2 | — |
| PRIMARY Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized) |
2880; 21.6 | — |
| PRIMARY Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized) |
724; 2.01 | — |
| PRIMARY Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized) |
— | — |
| PRIMARY Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized) |
— | — |
| SECONDARY Phase II: Percentage of Participants With AEs |
100; 100; 100; 97.4; 100; 100 | — |
| SECONDARY Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin |
0; 0; 7.9; 2.9 | — |
| SECONDARY Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab |
0; 0; 5.3; 5.6; 0; 0 | — |
| SECONDARY Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator |
64.1; 63.4; 42.5; 15.0; 65.0; 33.3 | 0.8817 |
| SECONDARY 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 |
65.0; 33.3; 35.7 | — |
| SECONDARY Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator |
79.5; 80.5; 47.5; 17.5; 85.0; 33.3 | 0.9523 |
| SECONDARY Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC |
76.9; 73.2; 42.5; 17.5; 85.0; 38.1 | 0.6574 |
| SECONDARY Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator |
46.2; 19.5; 20.0; 5.0; 20.0; 14.3 | — |
| SECONDARY Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC |
41.0; 36.6; 22.5; 2.5; 50.0; 23.8 | — |
| SECONDARY Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator |
79.5; 75.6; 45.0; 15.0; 80.0; 33.3 | 0.6225 |
| SECONDARY Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC |
74.4; 80.5; 40.0; 15.0; 80.0; 38.1 | 0.4835 |
| SECONDARY Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator |
89.7; 90.2; 70.0; 32.5; 90.0; 52.4 | 0.9390 |
| SECONDARY DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC |
62.5; 25.0; 42.9; 57.5 | 0.0005 sig |
| SECONDARY DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator |
12.665; 4.074; 16.099; 11.335 | 0.0245 sig |
| SECONDARY DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC |
10.908; 10.645; 25.758; 13.437 | 0.2451 |
| SECONDARY DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator |
7.491; 2.037; 5.125; 5.881 | <.0001 sig |
| SECONDARY DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC |
9.248; 3.713; 5.848; 6.965 | 0.0003 sig |
| SECONDARY Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator |
36.8 | — |
| SECONDARY Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator |
42.5 | — |
| SECONDARY Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC |
43.4 | — |
| SECONDARY Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator |
62.3 | — |
| SECONDARY Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC |
57.5 | — |
| SECONDARY Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator |
11.335 | — |
| SECONDARY Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC |
13.437 | — |
| SECONDARY Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator |
5.881 | — |
| SECONDARY Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC |
6.965 | — |
| SECONDARY Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator |
5.092 | — |
| SECONDARY Phase II NF Cohorts: Overall Survival (OS) |
12.320 | — |
| SECONDARY Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC |
35.7 | — |
| SECONDARY Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator |
9.5 | — |
| SECONDARY Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC |
14.3 | — |
| SECONDARY Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator |
38.1 | — |
| SECONDARY Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC |
33.3 | — |
| SECONDARY Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE |
653; 14.6; 667; 23.2; 659 | — |
| SECONDARY Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab |
33.9; 3.27; 36.0; 5.41; 39.2 | — |
| SECONDARY Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE |
0.590; 0.229; 0.316; 0.186; 0.256 | — |
| SECONDARY Plasma Concentration of Bendamustine |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Serum Concentration of Rituximab |
NA; NA; NA; NA; 182; 202 | — |
| SECONDARY Serum Concentration of Obinutuzumab |
NA; NA; NA; NA; 341; 221 | — |
| SECONDARY Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a |
676; 634; 697; 694; 763; 759 | — |
| SECONDARY Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b |
738; 725; 816; 841; 749; 721 | — |
| SECONDARY Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C |
622; 661; 703; 659; 36.7; 35.7 | — |
| SECONDARY Phase II: Cmax of Bendamustine and Rituximab in Arms B and D |
3.21; 3.85; 207; 183 | — |
| SECONDARY Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F |
692; 703; 845; 713; 33.3; 39.0 | — |
| SECONDARY Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized) |
— | — |
| SECONDARY Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a |
2830; 2110; 298; 214 | — |
| SECONDARY Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b |
2600; 2650; 267; 252 | — |
| SECONDARY Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C |
3.29; 3.62 | — |
| SECONDARY Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D |
2.86; 3.43 | — |
| SECONDARY Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F |
2.88; 4.10 | — |
| SECONDARY Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized) |
— | — |
| SECONDARY Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a |
11.3; 15.2; 6.05; 8.48 | — |
| SECONDARY Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b |
12.3; 12.1; 6.76; 7.17 | — |
| SECONDARY Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C |
47.9; 42.6 | — |
| SECONDARY Phase II: CL of Bendamustine and Rituximab in Arms B and D |
54.4; 46.4 | — |
| SECONDARY Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F |
61.3; 39.9 | — |
| SECONDARY Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized) |
— | — |
| SECONDARY Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a |
73.0; 82.7; 82.3; 76.6 | — |
| SECONDARY Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b |
77.2; 64.7; 87.5; 87.9 | — |
| SECONDARY Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C |
36.5; 34.3 | — |
| SECONDARY Phase II: Vss of Bendamustine and Rituximab in Arms B and D |
44.9; 33.2 | — |
| SECONDARY Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F |
51.2; 31.5 | — |
| SECONDARY Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized) |
— | — |
| SECONDARY Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F |
0.2; 0.5; 0.4; 0.6; 0.8; 0.3 | — |
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
Data sourced from ClinicalTrials.gov (NCT02257567). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.