A Phase I/II Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Patients With Diffuse Large B-Cell Lymphoma Following First-Line Immunotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 32
- 主要终点
- Percentage of Participants with Adverse Events
研究概览
简要总结
This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated 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
Consolidation Therapy (Cohort A)
Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).
干预措施: Mosunetuzumab Intravenous (IV) (Drug)
Consolidation Therapy (Cohort A)
Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).
干预措施: Tocilizumab (Drug)
Elderly/Unfit Previously Untreated Monotherapy (Cohort B)
Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
干预措施: Mosunetuzumab Intravenous (IV) (Drug)
Elderly/Unfit Previously Untreated Monotherapy (Cohort B)
Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
干预措施: Tocilizumab (Drug)
Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)
Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.
干预措施: Mosunetuzumab Subcutaneous (SC) (Drug)
Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)
Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.
干预措施: Polatuzumab Vedotin (Drug)
Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)
Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events
时间窗: Baseline through approximately 90 days after last study treatment
Positron Emission Tomography-Computed Tomography (PET-CT) Complete Response (CR) Rate at Time of Primary Response Assessment (PRA) According to Lugano 2014 Response Criteria (Cohort A)
时间窗: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
PET-CT Objective Response Rate (ORR) at PRA According to Lugano 2014 Response Criteria as Determined by the Investigator (Cohort B)
时间窗: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
PET-CT ORR at PRA According to the Lugano 2014 Criteria as Determined by an Independent Review Committee (IRC) (Cohort C)
时间窗: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
次要结局
- Maximum Serum Concentration (Cmax) of Mosunetuzumab SC(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Minimum Serum Concentration (Cmin) of Mosunetuzumab SC(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Volume of Distribution at Steady State (Vss) of Mosunetuzumab SC(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Clearance (CL) of Mosunetuzumab IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Maximum Serum Concentration (Cmax) of Mosunetuzumab IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Minimum Serum Concentration (Cmin) of Mosunetuzumab IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Area Under the Curve (AUC) of Polatuzumab Vedotin IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- End of Infusion Concentration (Ceoi) of Polatuzumab Vedotin IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Overall Survival (OS)(From the first study treatment to death from any cause)
- Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Physical Functioning and Fatigue (Cohorts B and C)(From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years))
- Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning (Cohorts B and C)(From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years))
- Area Under the Curve (AUC) of Mosunetuzumab IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Volume of Distribution at Steady State (Vss) of Mosunetuzumab IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Area Under the Curve (AUC) of Mosunetuzumab SC(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Clearance (CL) of Polatuzumab Vedotin IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Trough Concentration (Ctrough) of Polatuzumab Vedotin IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Duration of Response (DOR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)(From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years))
- Duration of Confirmed Response (DOCR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)(From the first occurrence of a documented CR to disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years))
- Progression-Free Survival (PFS) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)(From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years))
- Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C)(From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years))
- Clearance (CL) of Mosunetuzumab SC(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Minimum Serum Concentration (Cmin) of Polatuzumab Vedotin IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohorts B and C) and IRC (Cohort C)(6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days))
- Objective Response Rate (ORR), Defined as the Proportion of Participants with a Complete Response (CR) or Partial Response (PR) at PRA as Determined by the Investigator (Cohorts A and C)(Baseline through 2 years after PRA (up to a total of approximately 2.5 years))
- Best ORR (CR or PR at any time) During the Study Based on PET-CT and/or CT Scans as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)(Baseline through 2 years after PRA (up to a total of approximately 2.5 years))
- Anti-Drug Antibodies (ADAs) to Mosunetuzumab(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Volume of Distribution at Steady State (Vss) of Polatuzumab Vedotin IV(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))
- Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C)(From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years))
- Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C)(From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years))
- Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin (Cohort C)(At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days))