Phase 2
N=131
A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)
Non-Hodgkin's Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT02611323 ↗Enrolled (actual)
131
Serious AEs
37.4%
Results posted
Oct 2023
Primary outcome: Primary: Percentage of Participants With CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans — 100; 51.2; 25; 32.5 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Obinutuzumab (Drug); Rituximab (Drug); Polatuzumab Vedotin (Drug); Venetoclax (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Aug 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans |
100; 51.2; 25; 32.5 | — |
| PRIMARY FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
100; 100; 100; 100; 100; 100 | — |
| PRIMARY DLBCL Cohorts: Percentage of Participants With AEs and SAEs |
100; 100; 87.5; 97.5; 100; 66.7 | — |
| PRIMARY Number of Participants With Dose-Limiting Toxicities (DLTs) |
1; 0; 0; 0; 2; 1 | — |
| PRIMARY RP2D of Polatuzumab Vedotin |
1.8 | — |
| PRIMARY RP2D of Venetoclax |
800; 800 | — |
| SECONDARY Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans |
100; 51.2; 25.0; 32.5 | — |
| SECONDARY Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone |
62.5; 36.6; 16.7; 26.5 | — |
| SECONDARY Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone |
75.0; 29.3; 25.0; 22.5 | — |
| SECONDARY Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans |
100.0; 70.7; 25.0; 37.5 | — |
| SECONDARY Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans |
100.0; 75.6; 37.5; 42.5 | — |
| SECONDARY Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone |
87.5; 82.9; 25.0; 37.5 | — |
| SECONDARY Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone |
87.5; 85.4; 37.5; 45.0 | — |
| SECONDARY Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone |
100.0; 87.8; 50.0; 72.5 | — |
| SECONDARY Observed Serum Obinutuzumab Concentration |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Observed Serum Rituximab Concentration |
NA; NA; NA; NA; 199; 189 | — |
| SECONDARY Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Observed Plasma Venetoclax Concentration |
NA; 0.624; 0.247; 0.108; 0.244; 0.796 | — |
| SECONDARY Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin |
1; 0; 0; 0; 0; 0 | — |
Summary
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy will receive post-induction treatment with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.
Eligibility Criteria
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody (mAb) and for which no other more appropriate treatment option exists, as determined by the investigator
- For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 mAb and for which no curative option exists as determined by the investigator
- At least one bidimensionally measurable lesion
Exclusion Criteria
- Known CD20-negative status at relapse or progression
- Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
- Grade 3b FL
- History of transformation of indolent disease to DLBCL
- Current use of systemic corticosteroids greater than (>) 20 mg prednisone per day (or equivalent); or prior anti-cancer therapy to include: radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
- Central nervous system (CNS) disease
- Active infection
- Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star fruit within 3 days prior to first dose of venetoclax
- Positive for human immunodeficiency virus (HIV) or hepatitis B or C
- Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
- Poor hematologic, renal, or hepatic function
- Pregnant or lactating women
- Life expectancy <3 months
Data sourced from ClinicalTrials.gov (NCT02611323). 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.