An Open-Label, Multicenter, Phase I/II Trial Evaluating the Safety, Efficacy, and Pharmacokinetics of Escalating Doses of Mosunetuzumab (BTCT4465A) as a Single Agent and Combined With Atezolizumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 713
- 试验地点
- 35
- 主要终点
- Atezolizumab Serum Concentration
研究概览
简要总结
This is a Phase 1/2 dose-escalation study of BTCT4465A (Mosunetuzumab) administered as a single agent and in combination with atezolizumab in participants with relapsed or refractory B-cell NHL and CLL. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •B-cell hematologic malignancies expected to express the cluster of differentiation 20 (CD20) antigen who have relapsed after or failed to respond to at least one prior treatment regimen and for whom there is no available therapy expected to improve survival
- •Adequate hepatic, hematologic, and renal function
排除标准
- •Pregnant or lactating women
- •Monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, chemotherapy, or other investigational anti-cancer agent within 4 weeks prior to study drug
- •Treatment with radiotherapy within 2 weeks prior to the first BTCT4465A (Mosunetuzumab) administration
- •Systemic immunosuppressive medication within 2 weeks prior to study drug
- •Autologous stem cell transplantation (SCT) within 100 days prior to study drug, or any prior allogeneic SCT or solid organ transplantation
- •Autoimmune disease with the exception of controlled/treated hypothyroidism, disease-related immune thrombocytopenic purpura, or hemolytic anemia
- •History of central nervous system (CNS) lymphoma or other CNS disease
- •Significant cardiovascular or pulmonary disease
- •Hepatitis B or C or human immunodeficiency virus (HIV)
- •Receipt of a live attenuated vaccine within 4 weeks prior to study drug
- •Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first BTCT4465A (Mosunetuzumab) administration
研究组 & 干预措施
Dose Expansion
Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.
干预措施: BTCT4465A (Mosunetuzumab) IV (Drug)
Dose Escalation
Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level.
干预措施: BTCT4465A (Mosunetuzumab) IV (Drug)
Dose Escalation
Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level.
干预措施: Atezolizumab (Drug)
Dose Escalation
Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level.
干预措施: BTCT4465A (Mosunetuzumab) SC (Drug)
Dose Expansion
Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.
干预措施: Atezolizumab (Drug)
Dose Expansion
Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.
干预措施: BTCT4465A (Mosunetuzumab) SC (Drug)
结局指标
主要结局
Atezolizumab Serum Concentration
时间窗: Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)
Percentage of Participants with Complete Response as Assessed Using Standard Criteria for NHL
时间窗: Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal)
Maximum Tolerated Dose (MTD) of BTCT4465A (Mosunetuzumab)
时间窗: BTCT4465A (Mosunetuzumab) single agent: Cycle 1; BTCT4465A (Mosunetuzumab) in combination with atezolizumab: during the first cycle that BTCT4465A (Mosunetuzumab) and atezolizumab are administered concurrently (cycle length = 21 days)
Percentage of Participants With Adverse Events
时间窗: Cycle 1 Day 1 until 90 days after the last infusion (cycle length = 21 days; up to approximately 14 months)
BTCT4465A (Mosunetuzumab) Serum Concentration
时间窗: Baseline up to 30 days after the last infusion of BTCT4465A (Mosunetuzumab) (up to approximately 12 months)
次要结局
- Progression-Free Survival (PFS) as Assessed Using Standard Criteria for NHL(Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, withdrawal, or death from any cause))
- Overall Survival(Baseline until death from any cause (up to approximately 4 years))
- Duration of Response as Assessed Using Standard Criteria for NHL(Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal))
- European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Scores to Assess Health-Related Quality of Life (HRQoL)(Baseline until disease progression, start of new anti-cancer therapy, or withdrawal (up to approximately 4 years).)
- Objective Response Rate (ORR)(Baseline up to approximately 4 years (assessed at screening and then every 3 months until disease progression, start of new anti-cancer therapy, or withdrawal))