A Phase 2 Trial of PT2977 in Combination With Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 118
- 试验地点
- 10
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This is an open-label Phase 2 study which will evaluate the efficacy and safety of belzutifan in combination with cabozantinib in participants with advanced ccRCC. Belzutifan and cabozantinib will be administered orally once daily.
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
- •Has locally advanced or metastatic RCC with predominantly clear cell subtype
- •Has at least one measurable lesion as defined by RECIST version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Has adequate organ function defined as follows:
- •Absolute neutrophil count ≥ 1,000/µL, hemoglobin level ≥ 10 g/dL and platelet count ≥ 100,000/µL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at screening;
- •Serum creatinine level ≤ 2.0 × upper limit of normal (ULN)
- •Transaminase levels (AST/ALT) ≤ 3.0 × upper limit of normal (ULN); total bilirubin (TBILI) ≤ 1.5 mg/dL in the absence of Gilbert's disease *Cohort 1: Participants must not have received prior systemic therapy for advanced or metastatic ccRCC
- •Cohort 2: Participants must have received prior immunotherapy and no more than two prior treatments for advanced or metastatic ccRCC
排除标准
- •Has received prior treatment with belzutifan or other HIF2α inhibitors
- •Has received prior treatment with cabozantinib
- •Has had radiation therapy for bone metastases within two weeks of starting study drug
- •Has a history of untreated brain metastases or history of leptomeningeal disease or spinal cord compression
- •Has failed to recover from the reversible effects of prior anticancer therapy
- •Has uncontrolled or poorly controlled hypertension
- •Is receiving anticoagulant therapy
- •Has had any major cardiovascular event within 6 months prior to study drug administration
- •Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
- •Has had major surgery within 3 months before first study drug administration
- •Has an active infection requiring systemic treatment
- •Is participating in another therapeutic clinical trial
研究组 & 干预措施
Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)
Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.
干预措施: Belzutifan (Drug)
Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)
Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.
干预措施: Cabozantinib (Drug)
Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)
Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.
干预措施: Belzutifan (Drug)
Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)
Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to approximately 2 years
ORR is defined as the percentage of participants with a best confirmed response of Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as determined by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
次要结局
- Progression Free Survival (PFS)(Up to approximately 2 years)
- Cabozantinib Plasma Concentration(Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose)
- Number of participants discontinuing study treatment due to an Adverse Event (AE)(Up to approximately 2 years)
- Belzutifan Plasma Concentration(Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose)
- Belzutifan Metabolite Plasma Concentration(Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose)
- Duration of Response (DOR)(Up to approximately 2 years)
- Overall Survival (OS)(Up to approximately 2 years)
- Number of participants experiencing an Adverse Event (AE)(Up to approximately 2 years)
- Time to Response (TTR)(Up to approximately 2 years)