Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion

Description

Summary

The primary objective of this study is to compare belzutifan to everolimus with respect to 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) and to compare everolimus with respect to overall survival (OS). The hypothesis is that belzutifan is superior to everolimus with respect to PFS and OS.

Official Title

An Open-label, Randomized Phase 3 Study of MK-6482 Versus Everolimus in Participants With Advanced Renal Cell Carcinoma That Has Progressed After Prior PD-1/L1 and VEGF-Targeted Therapies

Keywords

Carcinoma, Renal Cell Hypoxia inducible Factor (HIF) Hypoxia inducible factor 1B (HIF-1B) Hypoxia inducible factor 2 alpha (HIF-2 alpha) Hypoxia inducible factor 2α (HIF-2α) Renal Cell Carcinoma (RCC) Kidney Cancer PT-2977 PT2977 MK6482 Carcinoma Everolimus Belzutifan

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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 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 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 moderate to severe hepatic impairment (Child-Pugh B or C).
  • Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
  • Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
  • Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan or everolimus) formulations.
  • Has received prior treatment with belzutifan or another hypoxia inducible factor 2α (HIF-2α inhibitor).
  • 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 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.

Locations

  • University of California San Diego Moores Cancer Center ( Site 1546) accepting new patients
    La Jolla California 92093-0698 United States
  • St Joseph Heritage Healthcare ( Site 1531) accepting new patients
    Santa Rosa California 95403 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Merck Sharp & Dohme Corp.
ID
NCT04195750
Phase
Phase 3
Study Type
Interventional
Last Updated