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-2a Related Genetic Alterations (MK-6482-015)
- Conditions
- Pheochromocytoma/ParagangliomaPancreatic Neuroendocrine TumorVon Hippel-Lindau DiseaseAdvanced Gastrointestinal Stromal TumorHIF-2a Mutated Cancers
- Registration Number
- NCT04924075
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 322
Inclusion Criteria:<br><br>Cohort A1: Pheochromocytoma/Paraganglioma (PPGL)<br><br> - Has documented histopathological diagnosis (local report) of pheochromocytoma or<br> paraganglioma Note: Participants are allowed to receive therapy in first line where<br> a satisfactory treatment option does not exist and if participants are not<br> candidates for systemic chemotherapy or have refused such therapy. There is no limit<br> on number of prior systemic therapies.<br><br>Locoregional therapies or adjuvant/neoadjuvant therapies are not considered a line of<br>prior systemic therapy<br><br> - Has locally advanced or metastatic disease that is not amenable to surgery or<br> curative intent treatment<br><br> - Has adequately controlled blood pressure defined as blood pressure =150/90 mm Hg<br> (=135/85 mm Hg for adolescents) and with no change in antihypertensive medications<br> (for participants with concomitant hypertension) for at least 2 weeks prior to start<br> of study treatment.<br><br>Cohort A2: Pancreatic Neuroendocrine Tumor (pNET)<br><br> - Has documented histopathological or cytopathological diagnosis (local report) of<br> well-differentiated, low, or intermediate grade (G1 or G2 pNET per 2017 World Health<br> Organization (WHO) classification and grading) pNET.<br><br> - Has locally advanced disease or metastatic disease that is:<br><br> 1. Not amenable for surgery, radiation, locoregional therapies or combination<br> modality of such treatments with curative intent.<br><br> 2. Experienced disease progression on or after at least 1 line of prior systemic<br> therapy that includes an approved targeted agent such as everolimus or<br> sunitinib. Participants who have received >3 prior systemic therapies will be<br> capped to =20% of the cohort.<br><br>Note: Chemoembolization/radiofrequency ablation/locoregional therapies,<br>neoadjuvant/adjuvant treatments, or somatostatin analog monotherapy or interferon<br>monotherapy will not count as 1 line of prior systemic therapy.<br><br>Cohorts A1, A2 and PPGL/pNET participants from Cohort D<br><br> - Has disease progression within the past 12 months from Screening.<br><br> - Has measurable disease per RECIST 1.1 by computed tomography (CT) or magnetic<br> resonance imaging (MRI) as assessed by local site investigator/radiology assessment<br> and verified by BICR.<br><br> 1. Irradiated lesions or lesions treated with locoregional therapies should not be<br> used as target lesions unless they clearly demonstrate growth since completion<br> of radiation.<br><br> 2. Metastatic lesions situated in the brain are not considered measurable and<br> should be considered nontarget lesions.<br><br> 3. Only lesions of the primary indication for the cohort may be evaluated for<br> measurability; other neoplastic lesions will be documented by the investigator<br> and this information provided to the independent reviewers to ensure that such<br> lesions are not included in the RECIST assessment.<br><br> 4. Participants who are adolescents (12-17 years of age) need to have a body<br> weight of 40 kilograms (kg) or more.<br><br>Cohort B1: von Hippel-Lindau (VHL) Disease-Associated Tumors<br><br> - Have a diagnosis of VHL disease as determined by a germline test (documented<br> germline VHL gene alteration) locally and/or clinical diagnosis.<br><br> - Have at least 1 measurable PPGL or pNET per RECIST 1.1 by CT or MRI as assessed by<br> local site investigator/radiology assessment and verified by BICR.<br><br> - Participants from China or Japan defined as participants of Chinese or Japanese<br> origin residing in mainland China or Japan respectively at the time of Screening,<br> must have at least 1 measurable RCC or PPGL or pNET per RECIST 1.1 as assessed by<br> local site investigator/radiology assessment and verified by BICR.<br><br> - Must be =18 years of age.<br><br>For Cohort B1 participants with PPGL<br><br> - Must not have pheochromocytoma >5 cm or paraganglioma >4 cm that requires immediate<br> surgery.<br><br> - Have adequately controlled blood pressure defined as blood pressure =150/90 mm Hg<br> and with no change in antihypertensive medications (for participants with<br> concomitant hypertension) for at least 2 weeks prior to start of study treatment.<br><br> - Must not have Metastatic or locally advanced, unresectable PPGL.<br><br> - Presence of concomitant VHL disease-associated tumors is permitted as long as they<br> do not require immediate surgery or intervention.<br><br>For Cohort B1 participants with pNET:<br><br> - Must not have lesion(s) located in the head of the pancreas must be >2 cm that<br> requires immediate surgery.<br><br> - Must not have lesion(s) located in the body or tail of the pancreas must be >3 cm<br> that requires immediate surgery.<br><br> - Must not have locally advanced, unresectable or metastatic pNET.<br><br> - Presence of concomitant VHL disease-associated tumors is permitted as long as they<br> do not require immediate surgery or intervention.<br><br>For Cohort B1 participants with renal cell carcinoma (RCC):<br><br> - Must not have lesion(s) >3 cm that requires immediate surgery.<br><br> - Must not have metastatic RCC.<br><br> - Presence of concomitant VHL disease-associated tumors is permitted as long as they<br> do not require immediate surgery or intervention.<br><br>For Cohort C participants with GIST (wt):<br><br> - Has documented histopathological diagnosis of GIST.<br><br> - Local test report documenting the absence of sensitizing mutations in both platelet<br> derived growth factor receptor alpha (PDGFRA) and receptor tyrosine kinase (c-KIT).<br><br> - Has locally advanced or metastatic disease that is not amenable to surgery or<br> curative intent treatment.<br><br>For Cohort D participants with advanced solid tumors with HIF-2a related genetic<br>alterations:<br><br> - Local test report documenting germline or somatic mutations in at least one of the<br> HIF-2a related genes.<br><br> - Has locally advanced or metastatic solid tumor that is not amenable to surgery or<br> curative intent treatment.<br><br> - Has progressed on/after standard therapy for advanced/metastatic disease.<br><br> - Male participants are eligible to participate if they agree to the following during<br> the intervention period and for at least 7 days after the last dose of study<br> intervention:<br><br> 1. Be abstinent from heterosexual intercourse as their preferred and usual<br> lifestyle (abstinent on a long-term and persistent basis) and agree to remain<br> abstinent OR<br><br> 2. Must agree to use contraception unless confirmed to be azoospermic<br> (vasectomized or secondary to medical cause as detailed below:<br><br> i. Agree to use a male condom plus partner use of an additional contraceptive method<br> when having penile-vaginal intercourse with a woman/women of childbearing potential<br> (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding<br> partner must agree to remain abstinent from penile-vaginal intercourse or use a male<br> condom during each episode of penile-vaginal penetration.<br><br> - A female participant is eligible to participate if she is not pregnant or<br> breastfeeding, and at least one of the following conditions applies:<br><br> 1. Is not a WOCBP OR<br><br> 2. Is a WOCBP and using a contraceptive method that is highly effective (with a<br> failure rate of <1% per year), or be abstinen
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Assessed by BICR;Time to Response (TTR) as Assessed by BICR;Disease Control Rate (DCR) as Assessed by BICR;Progressive Free Survival (PFS) as Assessed by BICR;Overall Survival (OS);Number of Participants Experiencing Adverse Events (AEs);Number of Participants Discontinuing Study Drug due to an AE;Time to Surgery (TTS)