A Phase Ia/Ib Open-Label, Multicenter Study Evaluating the Safety and Pharmacokinetics of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma, and as a Single Agent and in Combination With Rituximab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 41
- 试验地点
- 14
- 主要终点
- Percentage of Participants With Adverse Events
研究概览
简要总结
This is a Phase I open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity of tiragolumab administered as a single agent or in combination with atezolizumab and/or daratumumab or rituximab in participants with relapsed or refractory (R/R) multiple myeloma (MM) or R/R non-Hodgkin lymphoma (NHL).
详细描述
In the Phase Ia part of the study, tiragolumab is administered as a single agent in participants with R/R MM or R/R NHL.
In the Phase Ib part of the study, tiragolumab is administered in combination with atezolizumab and/or daratumumab in participants with R/R MM or with rituximab in participants with R/R NHL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •General Inclusion Criteria (All Participants):
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Life expectancy of >/= 12 weeks
- •Inclusion Criteria Specific to Arms A, C and E (R/R MM):
- •Arm A only: Must have R/R MM for which no established therapy for MM is appropriate and available or be intolerant to those established therapies
- •Arms C and E only: Participants with R/R MM who have received at least 3 prior lines of therapy.
- •Measurable disease defined by laboratory test results.
- •Inclusion Criteria Specific to Arms B and D (R/R NHL):
- •Participants with histologically confirmed B-cell NHL who have relapsed or failed to respond to at least two prior systemic treatment regimens and for which no suitable therapy of curative intent or higher priority exists.
- •Must have at least one bi-dimensionally measurable lesion.
排除标准
- •General Exclusion Criteria (All Participants):
- •Any anti-cancer therapy, whether investigational or approved, including chemotherapy, monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, hormonal therapy, and/or radiotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to initiation of study treatment
- •Prior treatment with any anti-TIGIT agent
- •Prior treatment with chimeric antigen receptor-T (CAR-T) therapy within 12 weeks before first study drug administration
- •Autologous Stem-Cell Transplantation (ASCT) within 100 days prior to first study drug administration
- •Active or history of autoimmune disease or immune deficiency
- •Known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection within 4 weeks prior to first study drug administration
- •Exclusion Criteria Specific to Arms A, C and E (R/R MM):
- •Primary or secondary plasma cell leukemia
- •Current or history of CNS involvement by MM
- •Exclusion Criteria Specific to Arms B and D (R/R NHL):
- •Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- •Current or history of CNS lymphoma
- •Current eligibility for ASCT
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Arm A: Tiragolumab R/R MM
Participants with relapsed or refractory (R/R) Multiple Myeloma (MM) will receive a single dose of 600 mg tiragolumab by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W).
干预措施: Tiragolumab (Drug)
Arm B: Tiragolumab R/R NHL
Participants with relapsed or refractory (R/R) non-Hodgkin Lymphoma (NHL) will receive a single dose of 600 mg tiragolumab by IV infusion Q3W.
干预措施: Tiragolumab (Drug)
Arm C: Tiragolumab + Daratumumab R/R MM
Participants with R/R MM will receive 600 mg tiragolumab Q3W + daratumumab by subcutaneous (SC) injection.
干预措施: Tiragolumab (Drug)
Arm C: Tiragolumab + Daratumumab R/R MM
Participants with R/R MM will receive 600 mg tiragolumab Q3W + daratumumab by subcutaneous (SC) injection.
干预措施: Daratumumab/rHuPH20 (Drug)
Arm D: Tiragolumab + Rituximab R/R NHL
Participants with R/R NHL will receive 600 mg tiragolumab Q3W + rituximab by IV infusion and SC injection (optional).
干预措施: Tiragolumab (Drug)
Arm D: Tiragolumab + Rituximab R/R NHL
Participants with R/R NHL will receive 600 mg tiragolumab Q3W + rituximab by IV infusion and SC injection (optional).
干预措施: Rituximab (Drug)
Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM
Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection.
干预措施: Tiragolumab (Drug)
Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM
Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection.
干预措施: Daratumumab/rHuPH20 (Drug)
Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM
Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events
时间窗: Through study completion, an average of 1 year
Determined according to the NCI CTCAE Version 5.0
次要结局
- Serum Concentration of Tiragolumab(Cycles 1, 2, 3, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years))
- Serum Concentration of Atezolizumab(Cycles 1, 2, 3, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years))
- ORR for R/R NHL(Through study completion, an average of 1 year)
- Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab(Cycles 1, 2, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years))
- Percentage of Participants With ADAs to Atezolizumab(Cycles 1, 2, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years))
- Objective Response Rate (ORR) for R/R MM(Through study completion, an average of 1 year)