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)

Pancreatic Neuroendocrine Tumor Clinical Trial

Official title:

A Phase 2 Study to Evaluate the Efficacy and Safety of Belzutifan (MK-6482, Formerly PT2977) Monotherapy in Participants With Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Advanced Solid Tumors With HIF-2α Related Genetic Alterations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04924075
• Other study ID #: 6482-015
• Secondary ID: MK-6482-015PT297
• Status: Recruiting
• Phase: Phase 2
• Start date: August 12, 2021
• Est. completion date: February 26, 2027

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study to evaluate the efficacy and safety of belzutifan monotherapy in participants with advanced pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumor (pNET), von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Advanced Solid Tumors With hypoxia inducible factor-2 alpha (HIF-2α) related genetic alterations. The primary objective of the study is to evaluate the objective response rate (ORR) of belzutifan per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 322
• Est. completion date: February 26, 2027
• Est. primary completion date: February 26, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

Cohort A1: Pheochromocytoma/Paraganglioma (PPGL)

• Has documented histopathological diagnosis (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 chemotherapy 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 surgery or curative intent treatment

• Has adequately controlled blood 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 hypertension) 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 grade (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 Screening.

• Has measurable disease per RECIST 1.1 by computed tomography (CT) or magnetic resonance imaging (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 pancreas 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 carcinoma (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-2a related genetic alterations:

• Local test report documenting germline or somatic mutations in at least one of the HIF-2a 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 dose 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 tissue sample or newly obtained core or excisional biopsy 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 specimen should be obtained from a nontarget lesion or archival tissue. Bone biopsies should not be submitted.

• Has an Eastern Cooperative Oncology 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.

Exclusion Criteria:

• Is unable to swallow orally administered medication or has a disorder that might affect the absorption of belzutifan.

• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years with the following exceptions:

Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.

• Participants with history of VHL disease (germline VHL mutation documented by a local test report or with clinical diagnosis) will be permitted provided concurrent lesions (other than the tumor type being assessed such as PPGL for Cohort A1 and pNET for Cohort A2) are localized without immediate need for intervention. Cohort D participants with VHL disease will not be eligible.

• Prior history of surgical resection(s) for concurrent localized VHL disease-associated tumors is allowed provided there is no history of metastatic disease from concurrent tumors; history of systemic therapy for concurrent tumors will be exclusionary.

• Participants with history of other genetic syndromes (such as those with succinate dehydrogenase subunit genes (SDHx) germline mutation or multiple endocrine neoplasia/MEN) will be allowed provided concurrent tumors (outside of the organ affected in Cohort A1, Cohort A2, C and D respectively) are localized and do not require immediate intervention; history of metastatic disease in concurrent tumors or history of systemic therapy for concurrent tumors will be exclusionary.

• Cohort B1 participants with concomitant central nervous system (CNS) hemangioblastoma must not require immediate surgery or intervention and must not be at risk of imminent neurological complications.

• Cohort B1 participants with concomitant retinal angiomas/retinal hemangioblastomas must not require immediate intervention.

• Cohort B1 participants with any concomitant tumors must not require immediate surgery or intervention.

• For Cohort B1 participants, history of any anticancer systemic therapy (including investigational agents) for any VHL disease-associated tumor or history of metastatic disease from any VHL disease-associated tumor or other non-VHL disease-related tumor(s) will be exclusionary.

• Has known CNS metastases and/or carcinomatous meningitis.

• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, or arterial bypass (CABG) or percutaneous transluminal coronary angioplasty (PTCA) =6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Concurrent uncontrolled hypertension defined as blood pressure >150/90 mm mercury (Hg) despite optimal antihypertensive medications within 2 weeks prior to the first dose of study treatment.

Note: Medically controlled arrhythmia stable on medication is permitted.

• Has any of the following: A pulse oximeter reading <92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.

• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.

• Has had major surgery =4 weeks prior to first dose of study intervention.

• Has received prior treatment (except somatostatin analogs for pNET participants) with chemotherapy, targeted therapy, biologics or other investigational therapy within the past 4 weeks of first dose of study intervention.

• Has received prior locoregional therapies or radiation within the past 4 weeks of first dose of study intervention.

• Has received prior treatment with Peptide Receptor Radionuclide Therapy (PRRT)/radionuclide therapy (such as 177Lu-Dotatate) or other radiopharmaceutical therapy within the past 12 weeks from Screening for participants with pNET.

• Has received meta-iodobenzylguanidine (MIBG) therapy or other radiopharmaceutical therapy within the past 12 weeks from Screening for participants with PPGL.

• Has received prior treatment with any HIF-2a inhibitor (including belzutifan).

• Has a known hypersensitivity to the study treatment and/or any of its excipients.

• Has toxicities from prior locoregional or systemic or any other therapies that is not recovered to Common Terminology Criteria for Adverse Events (CTCAE) =Grade 1 (with the exception of alopecia).

• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), or recombinant Erythropoietin (EPO) =28 days prior to the first dose of study intervention.

• Is currently receiving strong inhibitors of Cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study.

• Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study.

• Is currently enrolled in and receiving study therapy, was enrolled in a study of an investigational agent, and received study therapy or used an investigational device within 4 weeks (28 days) of the first dose of study intervention.

• Has an active infection requiring systemic therapy.

• Has a known history of human immunodeficiency virus (HIV) infection.

• Has a known history of hepatitis B or known active hepatitis C (HCV) infection.

• For Cohort A2, has a tumor histology consistent with poorly differentiated pNET, neuroendocrine carcinoma, or neuroendocrine tumor (NET) of nonpancreatic origin.

1. Poorly differentiated or high grade pancreatic pNET or pancreatic neuroendocrine carcinoma; mixed adenoneuroendocrine carcinoma of the pancreas or concurrent pancreatic ductal adenocarcinoma will not be allowed.

2. Neuroendocrine tumor of nonpancreatic origin such as gastrointestinal, lung/thoracic, unknown primary, or other organs (including adenocarcinoid/goblet cell carcinoid/small cell carcinoma/large cell carcinoma). Note: Neuroendocrine carcinoma of any origin is exclusionary.

• For Cohort A2, participants who have uncontrolled symptoms from functional pNETs at study entry.

• Has had an allogenic tissue/solid organ transplant.

• For Cohort B1 participants, metastatic disease identified at Screening.

• For Cohort C and GIST participants, clinically significant active bleeding (such as gastrointestinal [GI] bleeding), perforation, obstruction, and other disease-related complications, requiring emergency surgery.

• For Cohort D participants, VHL disease is exclusionary.

Related Conditions & MeSH terms

• Advanced Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors
• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Neuroendocrine Tumor
• Paraganglioma
• Pheochromocytoma
• Pheochromocytoma/Paraganglioma
• Von Hippel-Lindau Disease

Intervention

Drug:
• Belzutifan
Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.

Locations

Country	Name	City	State
Australia	The Royal Melbourne Hospital ( Site 1602)	Parkville	Victoria
Australia	Prince of Wales Hospital-Medical Oncology ( Site 1601)	Randwick	New South Wales
Canada	Tom Baker Cancer Center ( Site 0203)	Calgary	Alberta
Canada	Princess Margaret Cancer Centre ( Site 0202)	Toronto	Ontario
China	Peking University First Hospital-Urology ( Site 1900)	Beijing	Beijing
China	West China Hospital of Sichuan University ( Site 1906)	Cheng Du	Sichuan
China	Sun Yat-sen University Cancer Center ( Site 1905)	Guangzhou	Guangdong
China	Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904)	Shanghai	Shanghai
Denmark	Rigshospitalet ( Site 0304)	Copenhagen	Hovedstaden
Denmark	Rigshospitalet-Department of Endocrinology ( Site 0303)	Copenhagen	Hovedstaden
Denmark	Odense Universitetshospital ( Site 0302)	Odense	Syddanmark
France	Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)	Le Kremlin-Bicêtre	Paris
France	Hôpital Edouard Herriot-oncologie ( Site 0405)	Lyon	Rhone-Alpes
France	Institut Paoli-Calmettes-Oncology ( Site 0406)	Marseille	Bouches-du-Rhone
France	Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)	Paris
France	CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402)	Strasbourg	Alsace
France	Gustave Roussy ( Site 0403)	Villejuif	Ile-de-France
Germany	Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site	Berlin
Germany	Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505)	Düsseldorf	Nordrhein-Westfalen
Germany	Universitaetsklinikum Freiburg ( Site 0504)	Freiburg	Baden-Wurttemberg
Germany	Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division (	München	Bayern
Germany	Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500)	Würzburg	Bayern
Hungary	Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600)	Budapest
Israel	Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400)	Ramat Gan
Israel	Sourasky Medical Center ( Site 1401)	Tel Aviv
Italy	Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701)	Brescia
Italy	Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe	Milano
Italy	Ospedale San Raffaele-Oncologia Medica ( Site 0705)	Milano	Lombardia
Italy	University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704)	Naples	Campania
Italy	Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma ( Site 0703)	Verona
Japan	National Cancer Center Hospital ( Site 1802)	Chuo-ku	Tokyo
Japan	Kyoto University Hospital ( Site 1806)	Kyoto
Japan	Kochi Medical School Hospital ( Site 1807)	Nankoku	Kochi
Japan	Hokkaido University Hospital ( Site 1800)	Sapporo	Hokkaido
Japan	Tokyo Women's Medical University Adachi Medical Center ( Site 1803)	Tokyo
Japan	Yokohama City University Hospital-Department of Urology ( Site 1804)	Yokohama	Kanagawa
Netherlands	Universitair Medisch Centrum Utrecht ( Site 1530)	Utrecht
Russian Federation	Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)	Moscow	Moskva
Russian Federation	Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801)	Moscow	Moskva
Russian Federation	Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov (	Saint Petersburg	Leningradskaya Oblast
Russian Federation	Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803)	Saint Petersburg	Leningradskaya Oblast
Russian Federation	GBUZ Republican Clinical Oncological Dispensary ( Site 0804)	Ufa	Baskortostan, Respublika
Singapore	National Cancer Centre Singapore ( Site 1700)	Singapore	Central Singapore
Spain	Hospital Universitari Vall d'Hebron ( Site 1100)	Barcelona
Spain	Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103)	Madrid	Madrid, Comunidad De
Spain	MD Anderson Cancer Center-Oncology ( Site 1102)	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101)	Oviedo	Asturias
Sweden	Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204)	Gothenburg	Vastra Gotalands Lan
Sweden	Skanes University Hospital Lund ( Site 1200)	Lund	Skane Lan
Sweden	Karolinska Universitetssjukhuset Solna ( Site 1202)	Stockholm	Stockholms Lan
Sweden	Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)	Uppsala	Uppsala Lan
Turkey	Ankara Bilkent Sehir Hastanesi. ( Site 0904)	Ankara
Turkey	Hacettepe Universitesi-oncology hospital ( Site 0901)	Ankara
Turkey	Ege University Medicine of Faculty ( Site 0900)	Bornova	Izmir
Turkey	Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)	Istanbul
United Kingdom	Addenbrooke's Hospital ( Site 1309)	Cambridge	Cambridgeshire
United Kingdom	The Beatson West of Scotland Cancer Centre ( Site 1308)	Glasgow	Glasgow City
United Kingdom	Hammersmith Hospital-Medical Oncology ( Site 1304)	London	London, City Of
United Kingdom	Royal Free Hospital ( Site 1302)	London	England
United States	University of Michigan ( Site 0126)	Ann Arbor	Michigan
United States	Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site	Baltimore	Maryland
United States	National Institutes of Health ( Site 0125)	Bethesda	Maryland
United States	Massachusetts General Hospital ( Site 0111)	Boston	Massachusetts
United States	University of Texas MD Anderson Cancer Center ( Site 0112)	Houston	Texas
United States	University of Iowa ( Site 0104)	Iowa City	Iowa
United States	Cedars-Sinai Medical Center ( Site 0110)	Los Angeles	California
United States	Vanderbilt University Medical Center ( Site 0107)	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai ( Site 0123)	New York	New York
United States	Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)	Philadelphia	Pennsylvania
United States	Washington University-Internal Medicine/Oncology ( Site 0124)	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Netherlands,  Russian Federation,  Singapore,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)	ORR is the percentage of participants with complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions) until progressive disease (PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progression) or death due to any cause, whichever occurs first.	Up to approximately 5.5 years
Secondary	Duration of Response (DOR) as Assessed by BICR	DOR is the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 5.5 years
Secondary	Time to Response (TTR) as Assessed by BICR	TTR is defined as the time from first dose of belzutifan to first documented evidence of CR or PR.	Up to approximately 5.5 years
Secondary	Disease Control Rate (DCR) as Assessed by BICR	Disease control is a confirmed CR, PR, or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study).	Up to approximately 5.5 years
Secondary	Progressive Free Survival (PFS) as Assessed by BICR	PFS is the time from first dose of belzutifan to the first documented PD or death from any cause, whichever occurs first.	Up to approximately 5.5 years
Secondary	Overall Survival (OS)	OS is the time from first dose of belzutifan until death from any cause.	Up to approximately 5.5 years
Secondary	Number of Participants Experiencing Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 5.5 years
Secondary	Number of Participants Discontinuing Study Drug due to an AE	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 5.5 years
Secondary	Time to Surgery (TTS)	TTS is defined as the time from the first dose of belzutifan to the first documented surgical intervention or tumor reduction procedure.	Up to approximately 5.5 years

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary