A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma
- Conditions
- B-cell Non-Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT03677141
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 117
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding Mosunetuzumab Participants will receive M-CHOP up to the phase II recommended dose (RP2D). Phase Ib: M-CHP-Pola Dose-Finding Mosunetuzumab Participants will receive M-CHP-Pola up to the RP2D. Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort Mosunetuzumab Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. Phase II: M-CHOP 1L DLBCL Mosunetuzumab 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. Phase II: M-CHP-Pola 1L DLBCL Mosunetuzumab Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. Phase Ib: M-CHP-Pola Dose-Finding Doxorubicin Participants will receive M-CHP-Pola up to the RP2D. Phase Ib: M-CHP-Pola Dose-Finding Prednisone Participants will receive M-CHP-Pola up to the RP2D. Phase Ib: M-CHP-Pola Dose-Finding Tocilizumab Participants will receive M-CHP-Pola up to the RP2D. Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort Cyclophosphamide Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort Doxorubicin Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding Polatuzumab Vedotin Participants will receive M-CHOP up to the phase II recommended dose (RP2D). Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding Cyclophosphamide Participants will receive M-CHOP up to the phase II recommended dose (RP2D). Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding Doxorubicin Participants will receive M-CHOP up to the phase II recommended dose (RP2D). Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding Vincristine Participants will receive M-CHOP up to the phase II recommended dose (RP2D). Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding Prednisone Participants will receive M-CHOP up to the phase II recommended dose (RP2D). Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding Tocilizumab Participants will receive M-CHOP up to the phase II recommended dose (RP2D). Phase Ib: M-CHP-Pola Dose-Finding Polatuzumab Vedotin Participants will receive M-CHP-Pola up to the RP2D. Phase Ib: M-CHP-Pola Dose-Finding Cyclophosphamide Participants will receive M-CHP-Pola up to the RP2D. Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort Vincristine Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort Prednisone Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort Tocilizumab Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP. Phase II: M-CHP-Pola 1L DLBCL Polatuzumab Vedotin Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. Phase II: M-CHP-Pola 1L DLBCL Cyclophosphamide Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. Phase II: M-CHP-Pola 1L DLBCL Doxorubicin Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. Phase II: M-CHP-Pola 1L DLBCL Prednisone Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. Phase II: M-CHP-Pola 1L DLBCL Tocilizumab Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage. Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL Polatuzumab Vedotin Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage. Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL Rituxumab Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage. Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL Cyclophosphamide Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage. Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL Doxorubicin Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage. Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL Prednisone Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage. Phase II: M-CHOP 1L DLBCL Cyclophosphamide 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. Phase II: M-CHOP 1L DLBCL Doxorubicin 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. Phase II: M-CHOP 1L DLBCL Vincristine 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. Phase II: M-CHOP 1L DLBCL Prednisone 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. Phase II: M-CHOP 1L DLBCL Tocilizumab 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.
- Primary Outcome Measures
Name Time Method 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) 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 Outcome Measures
Name Time Method 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 is defined as a CR or PR at the time of primary assessment based on PET-CT, as determined by the investigator.
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 ORR is defined as a CR or PR at the time of primary assessment based on CT only, as determined by the investigator.
Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II) Up to approximately 50 months Best ORR was defined as CR or PR at any time on study and based on PET-CT or CT only as determined by the investigator.
Duration of Response (DOR) as Determined by the Investigator (Phase II) Up to approximately 50 months DOR is defined as the time from the first occurrence of a documented objective response to disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).
Progression-free Survival (PFS) as Determined by the Investigator (Phase II) Up to approximately 50 months PFS is defined as the time from randomization to the first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The earliest contributing event to PFS is reported. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment were censored at the date of randomization or first study treatment, plus 1 day).
PFS at 1 Year as Determined by the Investigator (Phase II) 1 year PFS at 1 year is defined as the proportion of participants with disease progression or relapse as determined by the investigator, or death from any cause within 1 year of randomization.
Event-free Survival (EFS) as Determined by the Investigator (Phase II) Up to 50 months EFS is defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).
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 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) Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).
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) Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).
Mosunetuzumab Serum Concentrations C1D1-C5D1
Trial Locations
- Locations (41)
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of California; Moores Cancer Center
🇺🇸La Jolla, California, United States
University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
🇺🇸Santa Monica, California, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Scroll for more (31 remaining)University of Alabama Birmingham🇺🇸Birmingham, Alabama, United States