A phase 2 study of Belzutifan (MK-6482) monotherapy in participants with Advanced Pheochromocytoma/Paraganglioma (PPGL) or Pancreatic Neuroendocrine Tumor (pNET).

Phase 1

• Conditions: Pheochromocytoma/Paraganglioma or Pancreatic Neuroendocrine Tumor.; MedDRA version: 20.1Level: LLTClassification code 10034876Term: PheochromocytomaSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10073860Term: ParagangliomaSystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10067518Term: Pancreatic neuroendocrine tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005028-13-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-07
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

Cohort A1: Pheochromocytoma/Paraganglioma (PPGL):
1. Has documented histopathological diagnosis (local report) of pheochromocytoma or paraganglioma.
2. Has locally advanced or metastatic disease that is not amenable to surgery or curative intent treatment.
3. Adequately controlled blood pressure defined as blood pressure = 150/90 mm Hg (=135/85 mm Hg for adolescents) and with no change in hypertension) for at least 2 weeks prior to start of study treatment.

Cohort A2: Pancreatic Neuroendocrine Tumor (pNET):
4. Has documented histopathological or cytopathological diagnosis (local report) of well-differentiated, low or intermediate grade (G1 or G2 pNET per 2017 WHO classification and grading) pNET.
5. Has locally advanced disease or metastatic disease that is:
a) Not amenable for surgery, radiation, locoregional therapies or combination modality of such treatments with curative intent.
b) Experienced disease progression on or after at least 1 line of prior systemic therapy that includes an approved targeted agent such as everolimus (mTOR inhibitor) or sunitinib (antiVEGF targeted agent). Participants who have received >3 prior systemic therapies will be capped to =20% of the cohort.

Cohorts A1 and A2:
6. Has disease progression within the past 12 months from screening.
7. Has measurable disease per RECIST v1.1 by CT or MRI as assessed by local site investigator/radiology assessment and verified in real time by BICR. BICR must confirm the presence of radiologically measurable
disease per RECIST 1.1 for the participant to be eligible for the study
a) Irradiated lesions or lesions treated with locoregional therapies should not be used as target lesions unless they clearly demonstrate growth since completion of radiation.
b) Metastatic lesions situated in the brain are not considered measurable and should be considered nontarget lesions.
c) 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.
8. Is male or female, 12 years of age inclusive (=40 kg for adolescents [12-17 years of age]), at the time of signing the informed consent.

For further inclusion criteria please refer to the protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 68

Exclusion Criteria

1. Is unable to swallow orally administered medication or has a disorder that might affect the absorption of belzutifan.
2. 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:
a) Participants with history of VHL disease will be permitted provided concurrent lesions (other than PPGL for Cohort A1 and pNET for Cohort A2) are localized without immediate need for intervention.
b) 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.
c) Participants with history of other genetic syndromes will be allowed provided concurrent tumors (outside of the organ affected in Cohort A1 and Cohort A2, 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.
3. Has known CNS metastases and/or carcinomatous meningitis.
4. 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
5. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, or arterial bypass (CABG) or 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 Hg despite optimal antihypertensive medications within 2 weeks prior to the first dose of study treatment.
6. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
7. Has had major surgery =4 weeks prior to first dose of study intervention.
8. Has received prior treatment (except somatostatin analogs) with chemotherapy, targeted therapy, or other investigational therapy within the past 4 weeks of study entry, or prior biologics or immunotherapy within the past 6 weeks of study entry.
9. Has received prior locoregional therapies or radiation within the past 4 weeks of study entry.
10. Has received prior treatment with PRRT/radionuclide therapy or other radiopharmaceutical therapy within the past 12 weeks from screening for participants with pNET.
11. Has received meta-iodobenzylguanidine (MIBG) therapy or other radiopharmaceutical therapy within the past 12 weeks from screening for participants with PPGL.
12. Has received prior treatment with any HIF-2a inhibitor (including belzutifan).
13. Has a known hypersensitivity to the study treatment and/or any of its excipients.
14. Has toxicities from prior locoregional or systemic or any other therapies that is not recovered to baseline or CTCAE =Grade 1 (with the exception of alopecia).

For further exclusion criteria please refer to the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified