An Open-label, Randomized Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or MK-1308A in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, as First-Line Treatment in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,854
- 试验地点
- 262
- 主要终点
- Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC).
The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants; and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.
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 histologically confirmed diagnosis of RCC with clear cell component.
- •Has received no prior systemic therapy for advanced ccRCC
- •Male participants are abstinent from heterosexual intercourse or agree to use contraception during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib.
- •Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) or use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last
- •Has adequately controlled blood pressure with or without antihypertensive medications
- •Has adequate organ function.
- •Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to randomization/allocation
排除标准
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has had major surgery, other than nephrectomy within 4 weeks prior to randomization
- •Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has received prior radiotherapy within 2 weeks prior to first dose of study intervention
- •Has hypoxia or requires intermittent supplemental oxygen or requires chronic supplemental oxygen
- •Has clinically significant cardiac disease within 12 months from first dose of study intervention
- •Has a history of interstitial lung disease
- •Has symptomatic pleural effusion; a participant who is clinically stable following treatment of this condition is eligible
- •Has preexisting gastrointestinal or non-gastrointestinal fistula
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- •Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •Has a history of noninfectious pneumonitis that required steroids or has current pneumonitis
- •Has an active infection requiring systemic therapy
- •Has a known history of human immunodeficiency virus (HIV) infection
- •Has a known history of Hepatitis B
- •Has radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel
- •Has clinically significant history of bleeding within 3 months prior to randomization
- •Has had an allogenic tissue/solid organ transplant
研究组 & 干预措施
Pembrolizumab + Belzutifan + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to ~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Belzutifan + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to ~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
干预措施: Belzutifan (Drug)
Pembrolizumab + Belzutifan + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to ~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
干预措施: Lenvatinib (Drug)
Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (co-formulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered IV Q6W for up to 18 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
干预措施: Lenvatinib (Drug)
Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 18 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 18 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
干预措施: Lenvatinib (Drug)
Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (co-formulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered IV Q6W for up to 18 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
干预措施: Pembrolizumab/Quavonlimab (Biological)
结局指标
主要结局
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 46 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR based on RECIST 1.1 will be presented.
Overall Survival (OS)
时间窗: Up to approximately 66 months
OS is defined as the time from randomization to death due to any cause.
次要结局
- Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 46 months)
- Number of Participants Who Experienced At least One Adverse Event (AE)(Up to approximately 66 months)
- Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 66 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 66 months)