A Phase 2 Study to Evaluate the Efficacy and Safety of Belzutifan (MK-6482, Formerly PT2977) Monotherapy in Participants With Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Advanced Solid Tumors With HIF-2α Related Genetic Alterations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 355
- 试验地点
- 168
- 主要终点
- Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
This is a study to evaluate the efficacy and safety of belzutifan monotherapy in participants with advanced pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumor (pNET), von Hippel-Lindau (VHL) disease-associated tumors, advanced wt (wild-type) gastrointestinal stromal tumor (wt GIST), or advanced solid tumors with hypoxia inducible factor-2 alpha (HIF-2α) related genetic alterations. The primary objective of the study is to evaluate the objective response rate (ORR) of belzutifan per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Male and female participants at least 12 years of age (at least 18 years of age for Cohort B1)
- •Diagnosis of one of the following: Advanced/metastatic pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumors (pNET), von Hippel-Lindau (VHL) disease associated localized tumors, or advanced wild-type gastrointestinal stromal tumor (wt GIST) or advanced solid tumors with Hypoxia Inducible Factor- 2 alpha subunit (HIF-2α) related genetic alterations
- •Cohort B1: VHL Disease-associated tumors:
- •Have a diagnosis of VHL disease as determined by a germline test locally and/or clinical diagnosis
- •Must be ≥18 years of age
- •Has a life expectancy of at least 3 months
排除标准
- •include but are not limited to the following:
- •Unable to swallow orally administered medication or has a disorder that might affect the absorption of belzutifan
- •History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- •Any of the following: A pulse oximeter reading <92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
- •Clinically significant cardiac disease, including unstable angina, acute myocardial infarction, or arterial bypass (CABG) or Percutaneous transluminal coronary angioplasty (PTCA) ≤6 months from study entry, or New York Heart Association Class III or IV congestive heart failure
- •Received prior treatment (except somatostatin analogs) with chemotherapy, targeted therapy, biologics, or other investigational therapy within the past 4 weeks of first dose of study intervention
研究组 & 干预措施
Belzutifan
Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.
干预措施: Belzutifan (Drug)
结局指标
主要结局
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 5.5 years
ORR is the percentage of participants with complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions) until progressive disease (PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progression) or death due to any cause, whichever occurs first.
次要结局
- Number of Participants Experiencing Adverse Events (AEs)(Up to approximately 5.5 years)
- Time to Response (TTR) as Assessed by BICR(Up to approximately 5.5 years)
- Time to Surgery (TTS)(Up to approximately 5.5 years)
- Progressive Free Survival (PFS) as Assessed by BICR(Up to approximately 5.5 years)
- Duration of Response (DOR) as Assessed by BICR(Up to approximately 5.5 years)
- Number of Participants Discontinuing Study Drug due to an AE(Up to approximately 5.5 years)
- Disease Control Rate (DCR) as Assessed by BICR(Up to approximately 5.5 years)
- Overall Survival (OS)(Up to approximately 5.5 years)