- Has unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC)
- Has received systemic treatment for locally advanced or metastatic RCC with a
Programmed cell death 1 ligand 1 (PD-1/L1) checkpoint inhibitor (at least 2 doses of a
PD-1/L1 checkpoint inhibitor) and a vascular endothelial growth factor (VEGF) targeted
therapy (including tyrosine kinase inhibitors or monoclonal antibodies) as
monotherapy, or in combination.
- Has received no more than 3 prior systemic regimens for locally advanced or metastatic
- A male participant must agree to use contraception during the treatment period and for
at least 95 days.
- 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 treatment period and for at least 95 days after the last dose of
- The participant (or legally acceptable representative if applicable) provides written
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 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 drug 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 (MK-6482 or everolimus) formulations.
- Has received prior treatment with MK-6482 or another hypoxia inducible factor 2α
- 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 first dose of study
- Has had major surgery within 3 weeks prior to first dose of study intervention.
- Has received a live vaccine within 30 days prior to the first dose of study drug.
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 the first dose of study intervention.
- 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.
- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 95 days
after the last dose of study intervention.