A Multicenter, Open-label, Randomized, Phase 1/2 Study of Belzutifan in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 13
- 主要终点
- Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of belzutifan monotherapy and belzutifan plus palbociclib combination therapy in participants with advanced clear-cell renal cell carcinoma (ccRCC) who experienced disease progression on or after receiving prior therapy. The study will establish the safety of belzutifan plus palbociclib and determine a recommended dosage of palbociclib for the combination therapy by ascending dose escalation.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 a histologically confirmed diagnosis of unresectable Stage IV (per American Joint Committee on Cancer [AJCC], 8th Edition) RCC with clear-cell component
- •Has had disease progression on or after having received at least 2 systemic treatments for unresectable Stage IV RCC with prior anti-programmed cell death 1 ligand 1 (PD-1/L1) and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination
- •Has measurable disease per RECIST 1.1 as assessed by the investigator and verified by blinded independent central review (BICR)
- •Has recovered from all AEs due to previous therapies
排除标准
- •Has hypoxia, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has clinically significant cardiac disease
- •Has moderate to severe hepatic impairment
- •Has a known history of human immunodeficiency virus (HIV) infection
- •Has a history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
- •Has received prior treatment of belzutifan or palbociclib
- •Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
- •Has had major surgery ≤3 weeks prior to first dose of study intervention
- •Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention
研究组 & 干预措施
Beltuzifan 120 mg + Palbociclib 125 mg
Participants receive beltuzifan 120 mg orally QD and palbociclib 125 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
干预措施: Palbociclib (Drug)
Beltuzifan 120 mg + Palbociclib 100 mg
Participants receive beltuzifan 120 mg orally QD and palbociclib 100 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
干预措施: Palbociclib (Drug)
Beltuzifan 120 mg + Palbociclib 125 mg
Participants receive beltuzifan 120 mg orally QD and palbociclib 125 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
干预措施: Belzutifan (Drug)
Beltuzifan 120 mg + Palbociclib 100 mg
Participants receive beltuzifan 120 mg orally QD and palbociclib 100 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
干预措施: Belzutifan (Drug)
Beltuzifan 120 mg + Palbociclib 75 mg
Participants receive beltuzifan 120 mg orally once per day (QD) and palbociclib 75 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
干预措施: Belzutifan (Drug)
Beltuzifan 120 mg + Palbociclib 75 mg
Participants receive beltuzifan 120 mg orally once per day (QD) and palbociclib 75 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
干预措施: Palbociclib (Drug)
结局指标
主要结局
Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
时间窗: Up to approximately 28 days
A DLT consists of one or more of the following toxicities: Grade (Gr) 3 or 4 hypoxia or dyspnea; Gr 3 or 4 nausea, vomiting, or diarrhea if persistent for \>48 hours despite therapy; Gr 3 or 4 cardiovascular, vascular, or thrombotic events; Nonhematologic AE ≥Gr 3 in severity with exceptions; Gr 3 rash that does not resolve within 2 weeks; Gr 3 nonhematologic toxicity if persisting despite optimal medical treatment; Gr 3 or 4 hematologic toxicities; Gr 3 or 4 febrile neutropenia; Gr 3 or 4 nonhematologic laboratory value; Any aspartate aminotransferase or alanine aminotransferase \>8x the upper limit of normal (ULN) or 5 to 8x ULN persisting for \>2 weeks; \>2 weeks delay in dosing due to intervention-related toxicity; Intervention-related toxicity causing intervention discontinuation in the first 28 days of dosing; Missing \>20% of intervention doses due to drug-related AEs; Gr 5 toxicity. The number of participants who experience at least one DLT will be reported.
Number of Participants Who Experience at Least One Adverse Event (AE)
时间窗: Up to approximately 4 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be reported.
Number of Participants Who Discontinue Study Treatment Due to an AE
时间窗: Up to approximately 4 years
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. The number of participants who discontinued from the study treatment due to an AE will be reported.
次要结局
未报告次要终点