A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Mosunetuzumab
- Conditions
- B-cell Non-Hodgkin Lymphoma
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 117
- Locations
- 41
- Primary Endpoint
- Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Intervention: Mosunetuzumab
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Intervention: Polatuzumab Vedotin
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Intervention: Cyclophosphamide
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Intervention: Doxorubicin
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Intervention: Vincristine
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Intervention: Prednisone
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
Intervention: Tocilizumab
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
Intervention: Mosunetuzumab
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
Intervention: Polatuzumab Vedotin
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
Intervention: Cyclophosphamide
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
Intervention: Doxorubicin
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
Intervention: Prednisone
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
Intervention: Tocilizumab
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Intervention: Mosunetuzumab
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Intervention: Cyclophosphamide
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Intervention: Doxorubicin
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Intervention: Vincristine
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Intervention: Prednisone
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Intervention: Tocilizumab
Phase II: M-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Mosunetuzumab
Phase II: M-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Polatuzumab Vedotin
Phase II: M-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Cyclophosphamide
Phase II: M-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Doxorubicin
Phase II: M-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Prednisone
Phase II: M-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Tocilizumab
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Polatuzumab Vedotin
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Rituxumab
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Cyclophosphamide
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Doxorubicin
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
Intervention: Prednisone
Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.
Intervention: Mosunetuzumab
Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.
Intervention: Cyclophosphamide
Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.
Intervention: Doxorubicin
Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.
Intervention: Vincristine
Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.
Intervention: Prednisone
Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC)
Time Frame: 6-8 weeks after either C6D1 or last dose of study treatment
The CR rate was defined as the percentage of participants with CR. Assessments were made according to the Lugano 2014 Response Criteria.
Secondary Outcomes
- CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II)(6-8 weeks after C6D1 or last dose of study treatment)
- Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II)(6-8 weeks after C6D1 or last dose of study treatment)
- ORR at PRA Based on CT Only as Determined by the Investigator (Phase II)(6-8 weeks after C6D1 or last dose of study treatment)
- Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II)(Up to approximately 50 months)
- Duration of Response (DOR) as Determined by the Investigator (Phase II)(Up to approximately 50 months)
- Progression-free Survival (PFS) as Determined by the Investigator (Phase II)(Up to approximately 50 months)
- PFS at 1 Year as Determined by the Investigator (Phase II)(1 year)
- Event-free Survival (EFS) as Determined by the Investigator (Phase II)(Up to 50 months)
- Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale(C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation))
- Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30)(C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation))
- Polatuzumab Vedotin Serum Concentrations(C2D1, C6D1)
- Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations(C1D1-C6D1)
- Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations(C1D1-C6D1)
- Mosunetuzumab Serum Concentrations(C1D1-C5D1)
- Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab(Cycles 1, 2, 6, 16, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment))
- Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin(Cycles 1, 2, 6, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment))