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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 117
- 试验地点
- 41
- 主要终点
- 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)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
干预措施: Mosunetuzumab (Drug)
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
干预措施: Polatuzumab Vedotin (Drug)
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
干预措施: Cyclophosphamide (Drug)
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
干预措施: Doxorubicin (Drug)
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
干预措施: Vincristine (Drug)
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
干预措施: Prednisone (Drug)
Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
干预措施: Tocilizumab (Drug)
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
干预措施: Mosunetuzumab (Drug)
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
干预措施: Polatuzumab Vedotin (Drug)
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
干预措施: Cyclophosphamide (Drug)
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
干预措施: Doxorubicin (Drug)
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
干预措施: Prednisone (Drug)
Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
干预措施: Tocilizumab (Drug)
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
干预措施: Mosunetuzumab (Drug)
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
干预措施: Cyclophosphamide (Drug)
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
干预措施: Doxorubicin (Drug)
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
干预措施: Vincristine (Drug)
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
干预措施: Prednisone (Drug)
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
干预措施: Tocilizumab (Drug)
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.
干预措施: Mosunetuzumab (Drug)
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.
干预措施: Polatuzumab Vedotin (Drug)
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Doxorubicin (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Tocilizumab (Drug)
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.
干预措施: Polatuzumab Vedotin (Drug)
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.
干预措施: Rituxumab (Drug)
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Doxorubicin (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Mosunetuzumab (Drug)
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Doxorubicin (Drug)
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.
干预措施: Vincristine (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
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)
时间窗: 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.
次要结局
- 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))