Clinical trial NCT05899049: A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, vs Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)-China Extension Study
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Renal Cell
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Hypoxia inducible factor (HIF)
Hypoxia inducible factor 1B (HIF-1B)
Hypoxia inducible factor 2 alpha (HIF-2 alpha)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2023-06-12
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 58 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 58 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
timeFrame: Up to approximately 58 months
measure: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
timeFrame: Up to approximately 58 months
measure: Number of Participants Who Experienced At least One Adverse Event (AE)
timeFrame: Up to approximately 58 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 58 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer hospital-Renal carcinoma and melanoma ( Site 6000)
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital ( Site 6009)
state: Chongqing
city: Guangzhou
country: China
facility: SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 6003)
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 6036)
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital ( Site 6007)
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital-Urology ( Site 6006)
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital ( Site 6002)
state: Hubei
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University-Urology ( Site 6025)
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University ( Site 6019)
state: Jiangxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University ( Site 6014)
state: Shaanxi
city: Cheng Du
country: China
facility: West China Hospital Sichuan University-Urology Surgery ( Site 6016)
state: Sichuan
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University ( Site 6032)
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University ( Site 6024)
state: Zhejiang
city: Jiaxing
country: China
facility: The First Hospital of Jiaxing ( Site 6033)
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital-Urology ( Site 6028)
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University-Urology Surgery ( Site 6021)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: