An Open-label, Randomized Phase 3 Study of Belzutifan Versus Everolimus in Participants With Advanced Renal Cell Carcinoma after Prior Therapy
- Conditions
- Advanced Renal Cell CarcinomaMedDRA version: 25.0Level: LLTClassification code: 10086821Term: Advanced renal cell carcinoma Class: 100000004848Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-506635-15-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 746
Has unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC)., Has had disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with both Programmed cell death 1 ligand 1 (PD-1/L1) checkpoint inhibitor and a vascular endothelial growth factor - tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination., Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC., A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of study intervention., A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP OR a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention for those randomized to belzutifan and for at least 8 weeks after the last dose of study intervention for those randomized to everolimus., The participant (or legally acceptable representative if applicable) has provided documented informed consent for the study., Has adequate organ function.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. (Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy are not excluded.), Has received prior treatment with everolimus or any other specific or selective target of rapamycin complex 1 (TORC1)/ phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor (e.g., temsirolimus) in the advanced disease setting., Has received any type of systemic anticancer antibody (including investigational antibody) within 4 weeks before randomization., Has received prior radiotherapy within 2 weeks prior to randomization., Has had major surgery within 3 weeks prior to randomization., Has received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed., Is currently receiving either strong (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study., Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g., bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study., Is currently participating in a study of an investigational agent or is currently using an investigational device., Has an active infection requiring systemic therapy., Has active bacillus tuberculosis (TB)., Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. (Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks (28 days) by repeat imaging.), Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization., Has a known history of human immunodeficiency virus (HIV) infection. (Testing for HIV at screening is only required if mandated by local health authority., Has a known history of Hepatitis B virus (HBV) (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (HCV) (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection., Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study medication administration, or New York Heart Association Class III or IV congestive heart failure. (Medically controlled arrhythmia stable on medication is permitted.), Has poorly controlled hypertension defined as systolic blood pressure (SBP) =150 mm Hg and/or diastolic blood pressure (DBP) =90 mm Hg., Has mode
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To compare belzutifan to everolimus with respect to PFS per RECIST 1.1 as assessed by BICR<br>2. To compare belzutifan to everolimus with respect to OS;Secondary Objective: To compare belzutifan to everolimus with respect to ORR based on RECIST 1.1 as assessed by BICR, To evaluate the DOR as assessed by BICR according to RECIST 1.1, To evaluate the safety and tolerability of belzutifan compared to everolimus, To evaluate TTD and change from baseline in HRQoL using the EORTC QLQ-C30 and the FKSI-DRS, To characterize health utility as measured using the EuroQoL EQ-5D-5L;Primary end point(s): Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR), Overall Survival (OS)
- Secondary Outcome Measures
Name Time Method