A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Point in Time Objective Response Prior to Surgery
研究概览
简要总结
The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.
详细描述
Sitravatinib is a receptor tyrosine kinase inhibitor (TKI) that targets multiple closely related receptor tyrosine kinase pathways including VEGFR, PDGFR, c-KIT, MET, and the TAM family of receptors (TYRO3, AXL, and MER). Nivolumab is a monoclonal antibody directed against PD-1 and blocks the interaction between PD-1 and its ligands, thereby releasing PD-1-mediated inhibition of T-cell proliferation (including cytotoxic CD8+ T-cells) and cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment the efficacy of nivolumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Imaging results consistent with locally-advanced RCC
- •Candidate for partial or complete nephrectomy as part of treatment plan.
- •Measurable disease per RECIST version 1.
- •ECOG performance status 0 or
- •Adequate bone marrow and organ function.
排除标准
- •Prior systemic anti-tumor treatment for RCC.
- •Patients who are receiving any other investigational agents.
- •Clinical status indicating that immediate surgery (within 6 weeks) is warranted regardless of whether neoadjuvant therapy is to be administered, as assessed by the treating surgeon.
- •Inability to undergo baseline tumor biopsy.
- •Active or prior documented autoimmune or immunocompromising conditions.
- •Uncontrolled hypertension.
研究组 & 干预措施
Sitravatinib and nivolumab
Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy.
干预措施: Sitravatinib (Drug)
Sitravatinib and nivolumab
Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Point in Time Objective Response Prior to Surgery
时间窗: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Number and percentage of participants who experienced a response prior to surgery in accordance with RECIST 1.1. * CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; * PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions; * Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD); * PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.
Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery
时间窗: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)
Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.
次要结局
- Time to Surgery(Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks))
- Disease Free Survival (DFS)(Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks))
- Change From Baseline in CD4+ T-cells in the Tumor(Baseline to date of surgery (maximum time to surgery was approximately 13 weeks))
- Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)(Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks))
- Change From Baseline in CD8+ T-cells in the Tumor(Baseline to date of surgery (maximum time to surgery was approximately 13 weeks))
- Blood Plasma Concentrations of Sitravatinib(Day 1 (pre-dose, and 30 minutes and 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose))
- Percentage Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor(Baseline to date of surgery (maximum time to surgery was approximately 13 weeks))
- Change From Baseline in Regulatory T-cells (Tregs) in the Tumor(Baseline to date of surgery (maximum time to surgery was approximately 13 weeks))
- Change From Baseline of Selected Cytokines in Peripheral Blood(Baseline to Day 43)
- Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor(Baseline to date of surgery (maximum time to surgery was approximately 13 weeks))
- Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor(Baseline to date of surgery (maximum time to surgery was approximately 13 weeks))