Belzutifan/​MK-6482 for the Treatment of Advanced Pheochromocytoma/​Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)

• Drug: Belzutifan

Inclusion Criteria

Cohort A1: Pheochromocytoma/Paraganglioma (PPGL)

– Has documented histopathological diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results (local report) of pheochromocytoma or paraganglioma Note: Participants are allowed to receive therapy in first line where a satisfactory treatment option does not exist and if participants are not candidates for systemic chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells or have refused such therapy. There is no limit on number of prior systemic therapies.

Locoregional therapies or adjuvant/neoadjuvant therapies are not considered a line of prior systemic therapy

• Has locally advanced or metastatic disease that is not amenable to surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence or curative intent treatment
• Has adequately controlled bloodthe red bodily fluid that transports oxygen and other nutrients around the body pressure defined as blood pressure ≤150/90 mm Hg (≤135/85 mm Hg for adolescents) and with no change in antihypertensive medications (for participants with concomitant hypertensionhigh blood pressure) for at least 2 weeks prior to start of study treatment.

Cohort A2: Pancreatic Neuroendocrine Tumor (pNET)

• Has documented histopathological or cytopathological diagnosis (local report) of well-differentiated, low, or intermediate gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells (G1 or G2 pNET per 2017 World Health Organization (WHO) classification and grading) pNET.
• Has locally advanced disease or metastatic disease that is:
  1. Not amenable for surgery, radiation, locoregional therapies or combination modality of such treatments with curative intent.
  2. Experienced disease progression on or after at least 1 line of prior systemic therapy that includes an approved targeted agent such as everolimus or sunitinib. Participants who have received >3 prior systemic therapies will be capped to ≤20% of the cohort.

Note: Chemoembolization/radiofrequency ablation/locoregional therapies, neoadjuvant/adjuvant treatments, or somatostatin analog monotherapy or interferon monotherapy will not count as 1 line of prior systemic therapy.

Cohorts A1, A2 and PPGL/pNET participants from Cohort D

• Has disease progression within the past 12 months from Screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening.
• Has measurable disease per RECIST 1.1 by computed tomography (CT) or magnetic resonance imagingtests that create detailed images of areas inside the body (MRI) as assessed by local site investigator/radiology assessment and verified by BICR.
  1. Irradiated lesions or lesions treated with locoregional therapies should not be used as target lesions unless they clearly demonstrate growth since completion of radiation.
  2. Metastatic lesions situated in the brain are not considered measurable and should be considered nontarget lesions.
  3. Only lesions of the primary indication for the cohort may be evaluated for measurability; other neoplastic lesions will be documented by the investigator and this information provided to the independent reviewers to ensure that such lesions are not included in the RECIST assessment.
  4. Participants who are adolescents (12-17 years of age) need to have a body weight of 40 kilograms (kg) or more.

Cohort B1: von Hippel-Lindau (VHL) Disease-Associated Tumors

• Have a diagnosis of VHL disease as determined by a germline test (documented germline VHL gene alteration) locally and/or clinical diagnosis.
• Have at least 1 measurable PPGL or pNET per RECIST 1.1 by CT or MRI as assessed by local site investigator/radiology assessment and verified by BICR.
• Participants from China or Japan defined as participants of Chinese or Japanese origin residing in mainland China or Japan respectively at the time of Screening, must have at least 1 measurable RCC or PPGL or pNET per RECIST 1.1 as assessed by local site investigator/radiology assessment and verified by BICR.
• Must be ≥18 years of age.

For Cohort B1 participants with PPGL

• Must not have pheochromocytoma >5 cm or paraganglioma >4 cm that requires immediate surgery.
• Have adequately controlled blood pressure defined as blood pressure ≤150/90 mm Hg and with no change in antihypertensive medications (for participants with concomitant hypertension) for at least 2 weeks prior to start of study treatment.
• Must not have Metastatic or locally advanced, unresectable PPGL.
• Presence of concomitant VHL disease-associated tumors is permitted as long as they do not require immediate surgery or intervention.

For Cohort B1 participants with pNET:

• Must not have lesion(s) located in the head of the pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation must be >2 cm that requires immediate surgery.
• Must not have lesion(s) located in the body or tail of the pancreas must be >3 cm that requires immediate surgery.
• Must not have locally advanced, unresectable or metastatic pNET.
• Presence of concomitant VHL disease-associated tumors is permitted as long as they do not require immediate surgery or intervention.

For Cohort B1 participants with renal cell carcinomacancer arising from tissues that line organs (RCC):

• Must not have lesion(s) >3 cm that requires immediate surgery.
• Must not have metastatic RCC.
• Presence of concomitant VHL disease-associated tumors is permitted as long as they do not require immediate surgery or intervention.

For Cohort C participants with GIST (wt):

• Has documented histopathological diagnosis of GIST.
• Local test report documenting the absence of sensitizing mutations in both platelet derived growth factor receptor alpha (PDGFRA) and receptor tyrosine kinase (c-KIT).
• Has locally advanced or metastatic disease that is not amenable to surgery or curative intent treatment.

For Cohort D participants with advanced solid tumors with HIF-2α related genetic alterations:

• Local test report documenting germline or somatic mutations in at least one of the HIF-2α related genes.
• Has locally advanced or metastatic solid tumor that is not amenable to surgery or curative intent treatment.
• Has progressed on/after standard therapy for advanced/metastatic disease.
• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dosethe amount of medication taken of study intervention:
  1. 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
  2. Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:

  i. Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman/women of childbearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  1. Is not a WOCBP OR
  2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), for at least 30 days after the last dose of study intervention.
• Submit an archival tumor tissuea group of cells that work together to perform a function sample or newly obtained core or excisional biopsyremoval of a section of tissue to analyse for cancer cells of a tumor lesion (not previously irradiated). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue if the lesion is accessible and a biopsy is not clinically contraindicated.

Note: If participant has only 1 measurable lesion per RECIST 1.1, the biopsy specimena sample for investigating (e.g. blood, stools, urine, sputum etc.) should be obtained from a nontarget lesion or archival tissue. Bone biopsies should not be submitted.

• Has an Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status of either 0 or 1, as assessed within 7 days of treatment initiation.
• Has adequate organ function.
• Has a life expectancy of at least 3 months.