Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma

1. Must have a histologically confirmed diagnosis of locally
advanced/metastatic RCC with clear cell component (with or without sarcomatoid
features) 2. Has measurable disease per RECIST 1.1 as assessed by BICR. 3.
Submit an archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are
preferred to slides. Newly obtained biopsies are preferred to archived tissue.
4. Has experienced disease progression on or after having received first-line
systemic treatment for locally advanced or metastatic RCC with prior
anti-PD-1/L1 + anti-CTLA4 combination or anti-PD-1/L1 + VEGF-targeted TKI
combination. - PD-1/L1 checkpoint inhibitor-based combination regimens (with
either VEGFtargeted TKI or anti-CTLA-4) treatment progression is defined by
meeting ALL of the following criteria: o Has received at least 2 doses of an
anti-PD-1/L1 mAb. o Has demonstrated radiographic disease progression during or
after an anti-PD- 1/L1 mAb as assessed by investigator. - If the participant
has received >1 prior regimen, there must have been demonstrated radiographic
disease progression after the most recently received regimen. 5. Has received
no more than 3 prior systemic regimens for locally advanced or metastatic RCC.
6. Is male or female, who is at least 18 years of age at the time of signing
the informed consent. 7. Has a KPS score of at least 70% [Karnofsky, D. A., et
al 1948] assessed within 10 days prior to the first dose of study intervention.
8. Male participants are eligible to participate if they agree to the following
during the intervention period and for at least 5 days after the last dose of
study intervention: • Be abstinent from heterosexual intercourse as their
preferred and usual lifestyle (abstinent on a long term and persistent basis)
and agree to remain abstinent OR • Must agree to use contraception unless
confirmed to be azoospermic (vasectomized or secondary to medical cause) as
detailed below: - Agree to use a male condom plus partner use of an additional
contraceptive method when having penile-vaginal intercourse with a WOCBP who is
not currently pregnant. • Male participants must also agree to use male condom
when engaging in any activity that allows for passage of ejaculate to another
person of any sex. • Contraceptive use by men should be consistent with local
regulations regarding the methods of contraception for those participating in
clinical studies. 9. A female participant is eligible to participate if she is
not pregnant or breastfeeding, and at least one of the following conditions
applies: • Is not a WOCBP OR • Is a WOCBP and using a contraceptive method that
is highly effective (with a failure rate of <1% per year), with low user
dependency, or be abstinent from heterosexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis), during the
intervention period and for at least 30 days after the last dose of study
intervention. The investigator should evaluate the potential for contraceptive
method failure (ie, noncompliance, recently initiated) in relationship to the
first dose of study intervention. • A WOCBP must have a negative highly
sensitive pregnancy test (urine or serum as required by local regulations)
within 24 hours before the first dose of study intervention. • If a urine test
cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy
test is required. In such cases, the participant must be excluded from
participation if the serum pregnancy result is positive. • Additional
requirements for pregnancy testing during and after study intervention • The
investigator is responsible for review of medical history, menstrual history,
and recent sexual activity to decrease the risk for inclusion of a woman with
an early undetected pregnancy. • Contraceptive use by women should be
consistent with local regulations regarding the methods of contraception for
those participating in clinical studies. 10. The participant (or legally
acceptable representative if applicable) provides written informed
consent/assent for the study. The participant may also provide consent/assent
for FBR. However, the participant may participate in the main study without
participating in FBR. 11. Has adequate organ function, all screening laboratory
tests should be performed within 10 days prior to the first dose of study
intervention.

1. A WOCBP who has a positive urine pregnancy test within 24 hours prior to
randomization (see Appendix 5). If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required. 2. Has any of
the following: - Hypoxia as defined by a pulse oximeter reading <92% at rest,
or - Requires intermittent supplemental oxygen, or - Requires chronic
supplemental oxygen. 3. Has a known additional malignancy that is progressing
or has required active treatment within the past 3 years. 4. Has known CNS
metastases and/or carcinomatous meningitis. 5. Has clinically significant
cardiac disease, including unstable angina, acute myocardial infarction <=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. 6. Has moderate to severe hepatic impairment
(Child-Pugh B or C). 7. Received colony-stimulating factors (eg, G-CSF, GM-CSF
or recombinant EPO) <=28 days prior to the first dose of study intervention. 8.
Has a known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the study. 9. Is unable to swallow orally
administered medication or has a gastrointestinal disorder affecting absorption
(eg, gastrectomy, partial bowel obstruction, malabsorption). 10. Has known
hypersensitivity or allergy to the active pharmaceutical ingredient or any
component of the study intervention (MK-6482) formulations. 11. Has received
prior treatment with MK-6482 or another HIF-2α inhibitor. 12. Has received any
type of small molecule kinase inhibitor (including investigational kinase
inhibitor) <=2 weeks before randomization. 13. Has received any type of systemic
anticancer antibody (including investigational antibody) <=4 weeks before
randomization. 14. Has received prior radiotherapy <=2 weeks prior to first dose
of study intervention. Participants must have recovered from all
radiation-related toxicities and not require corticosteroids. A 1-week washout
is required for palliative radiation (<=2 weeks of radiotherapy) to non-CNS
disease. 15. Has had major surgery <=3 weeks prior to first dose of study
intervention. 16. Is currently receiving either strong (phenobarbital,
enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine,
nevirapine and St John*s Wort) or moderate (eg, bosentan, efavirenz, modafinil)
inducers of CYP3A4 that cannot be discontinued for the duration of the study.
17. Is currently participating in a study of an investigational agent or is
currently using an investigational device. 18. Has an active infection
requiring systemic therapy. 19. Has active TB. 20. Has a diagnosis of
immunodeficiency. 21. Has a known history of HIV infection. 22. Has a known
history of HBV (defined as HBsAg reactive) or known active HCV (defined as HCV
RNA [qualitative] is detected) infection. 23. Has a history or current evidence
of any condition, therapy, or laboratory abnormality that might confound the
results of the study, interfere with the participant*s participation for the
full duration of the study, or is not the best interest of the participant to
participate, in the opinion of the treating investigator.