Paraganglioma

Drug(s)/Mechanism:
Belzutifan

Eligiblity information:
Cohort B1 specific inclusion criteria:

1. Have a diagnosis of VHL disease as determined by a germline test (documented germline VHL gene alteration) locally and/or clinical diagnosis, which can be made in the
following instances:
a. in a participant with a family history of VHL disease and at least one of the characteristic VHL-related tumors (eg, retinal HBs, CNS HBs, clear cell RCCs, pNETs, and endolymphatic sac tumors).
b. in the presence of 2 or more retinal or CNS HBs.
c. in the presence of 1 retinal or CNS HB, plus at least 1 of the characteristic VHLrelated visceral tumors, excluding renal and epididymal cysts.

2. 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. BICR must verify the
presence of radiologically measurable disease per RECIST 1.1 for either PPGL or pNET for the participant to be eligible for the study.

3. For Cohort B1 participants with PPGL:
a. No pheochromocytoma >5 cm or paraganglioma >4 cm that requires immediate surgery.
b. Participants should have adequately controlled BP defined as BP 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.
c. Metastatic or locally advanced, unresectable PPGL will be exclusionary.
d. Presence of concomitant VHL disease associated tumors is permitted as long as they do not require immediate surgery or intervention as applicable (see exclusion criteria #2d-2g).

4. For Cohort B1 participants with pNET:
a. No lesion(s) located in the head of the pancreas must be >2 cm that requires immediate surgery.
b. No lesion(s) located in the body or tail of the pancreas must be >3 cm that requires immediate surgery.
c. Locally advanced, unresectable or metastatic pNET will be exclusionary.
d. Presence of concomitant VHL disease associated tumors is permitted as long as they do not require immediate surgery or intervention as applicable (see exclusion criteria #2d-2g).

5. For Cohort B1 participants with RCC:
a. No lesion(s) must be >3 cm that requires immediate surgery.
b. Metastatic RCC will be exclusionary.
c. Presence of concomitant VHL disease associated tumors is permitted as long as they do not require immediate surgery or intervention as applicable (see exclusion criteria #2d-2g).

6. For Cohort D participants with advanced solid tumors with HIF-2A related genetic alterations:
a. Local test report documenting germline or somatic mutations in at least one of the HIF-2A related genes (HIF-2A/EPAS1, FH, SDHA, SDHB, SDHC, SDHD, SDHAF2, EGLN1, EGLN2, MDH2, ELOC/TCEB1).
b. Has locally advanced or metastatic solid tumor that is not amenable to surgery or curative intent treatment.
c. Participants must have progressed on/after standard therapy for advanced/metastatic disease. More than 3 prior therapies will not be allowed for this cohort in the advanced/metastatic setting.

For pre-screening, please contact: Message Basket: VICC RESEARCH REFERRALS/ELIGIBILITY