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)
Overview
- Phase
- Phase 3
- Intervention
- Pembrolizumab
- Conditions
- Carcinoma, Renal Cell
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 249
- Locations
- 17
- Primary Endpoint
- 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)
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
The goal of this China extension 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 Chinese 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.
Detailed Description
The China extension study will include participants previously enrolled in China in the global study for MK-6482-012 (NCT04736706) plus those enrolled during the China extension enrollment period. A total of approximately 249 Chinese participants will be enrolled.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Pembrolizumab
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.
Intervention: Belzutifan
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.
Intervention: Lenvatinib
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.
Intervention: Pembrolizumab/Quavonlimab
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.
Intervention: Lenvatinib
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.
Intervention: Pembrolizumab
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.
Intervention: Lenvatinib
Outcomes
Primary Outcomes
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)
Time Frame: Up to approximately 58 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)
Time Frame: Up to approximately 58 months
OS is defined as the time from randomization to death due to any cause.
Secondary Outcomes
- Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 58 months)
- Number of Participants Who Experienced At least One Adverse Event (AE)(Up to approximately 58 months)
- Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR(Up to approximately 58 months)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 58 months)