A Phase 1/1b Study of Sitravatinib in Combination With Nivolumab and Ipilimumab in Patients With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma or Other Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Frequency of patients experiencing treatment-emergent AEs
研究概览
简要总结
Study 516-008 is an open-label Phase 1 dose escalation/Phase 1b dose expansion study evaluating the safety and tolerability, clinical activity, and PK of sitravatinib in combination with nivolumab and ipilimumab for the treatment of ccRCC and potentially other solid tumor types.
详细描述
Sitravatinib is a spectrum-selective receptor tyrosine kinase (RTK) inhibitor that inhibits several closely related RTKs including the TAM family (Tyro3/Axl/MERTK), VEGFR2, KIT, and MET.
NIVO/IPI are monoclonal antibodies (mAbs) that inhibit the immune checkpoint proteins programmed death receptor-1 (PD-1) and cytotoxic T- lymphocyte antigen-4 (CTLA-4), respectively.
The current study is designed to evaluate the triple combination of sitravatinib plus NIVO/IPI in patients with solid tumor malignancies that have shown favorable responses to NIVO/IPI combinations in previous clinical trials. Combining sitravatinib and NIVO/IPI is predicted to have complementary effects in triggering a tumor-directed immune response.
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
- •Confirmed diagnosis of Clear-Cell Renal Cell Carcinoma (for initial cohorts under consideration)
- •No prior treatment with systemic therapy (for initial cohorts under consideration)
- •Adequate bone marrow and organ function
排除标准
- •Known or suspected presence of other cancer
- •Brain metastases (for initial cohorts under consideration)
- •Carcinomatous meningitis
- •Immunocompromising conditions
- •Impaired heart function
- •Active or prior documented autoimmune disease
研究组 & 干预措施
Phase 1: Dose Escalation
Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
干预措施: Sitravatinib (Drug)
Phase 1: Dose Escalation
Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
干预措施: Nivolumab (Drug)
Phase 1: Dose Escalation
Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment.
干预措施: Ipilimumab (Drug)
Phase 1b Dose Escalation Cohort A
Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
干预措施: Sitravatinib (Drug)
Phase 1b Dose Escalation Cohort A
Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
干预措施: Nivolumab (Drug)
Phase 1b Dose Escalation Cohort A
Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment
干预措施: Ipilimumab (Drug)
Phase 1b Dose Escalation Cohort B
Patients with favorable-risk RCC with clear cell component for first-line treatment.
干预措施: Sitravatinib (Drug)
Phase 1b Dose Escalation Cohort B
Patients with favorable-risk RCC with clear cell component for first-line treatment.
干预措施: Nivolumab (Drug)
Phase 1b Dose Escalation Cohort B
Patients with favorable-risk RCC with clear cell component for first-line treatment.
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Frequency of patients experiencing treatment-emergent AEs
时间窗: Through study completion, an average of 12 months
Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment
次要结局
- Progression-free Survival (PFS)(Through duration of study, average of 10 months)
- Objective Response Rate (ORR) in accordance with RECIST v1.1(Through duration of study, average of 10 months)
- Duration of Response (DOR)(Through duration of study, average of 10 months)