A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)

Solid Tumor Clinical Trial

Official title:

A Phase 1, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02974738
• Other study ID #: 6482-001
• Secondary ID: PT2977-101MK-648
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 7, 2016
• Est. completion date: April 14, 2025

Study information

• Verified date: September 2022
• Source: Peloton Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to identify the maximum tolerated dose (MTD) of belzutifan Tablets and/or the recommended Phase 2 dose (RP2D) of belzutifan Tablets in patients with advanced solid tumors

Description:

Part 1A: This is a Phase 1, multiple-dose, dose-escalation trial of belzutifan Tablets, where patients with advanced solid tumors will be assigned to sequential dose cohorts. Patient safety will be monitored with frequent physical examinations, vital sign measurements, electrocardiograms (ECGs), and hematology and chemistry laboratory studies, and by recording all adverse events (AEs). Blood will be obtained for analysis of the concentration of belzutifan and to assess biomarkers.

Part 1B: Once the MTD and/or the RP2D is achieved, and expansion cohort of 50 patients with advanced clear cell renal cell carcinoma (ccRCC) will be enrolled.

Part 2: After determination of the MTD/RP2D, up to 25 patients with other specified solid tumors may be enrolled. Up to 3 different tumor types may be included in this part of the study.

Part 2A: A cohort of 25 patients with glioblastoma (GBM)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: April 14, 2025
• Est. primary completion date: January 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a diagnosis of locally advanced or metastatic solid tumor

• Is of age = 18 years

• Has a life expectancy of = 6 months

• Has adequate organ function

• If a female patient, must not be pregnant or breastfeeding and not a woman of childbearing potential (WOCBP) OR a WOCBP who uses contraception or is abstinent from heterosexual intercourse during the study and for a minimum of 30 days after the last study drug administration, or if a male patient, must be abstinent from heterosexual intercourse OR agree to use contraception

• Able to swallow oral medications

Additional Inclusion Criteria for GBM cohort

• Must have histologically confirmed glioblastoma, IDH-wild type that is first recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria

• Must have archival tumor tissue available from a previous surgery for glioblastoma

• Must have measurable (defined as at least 1 cm x 1 cm) contrast-enhancing lesion by MRI imaging within 21 days of starting treatment

• Must be able to undergo MRI of the brain with gadolinium. Patients must be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days) prior to this baseline MRI

• Must have recovered from prior therapy to grade =1 severity (except for alopecia and lymphocytopenia) National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Exclusion Criteria:

• Has a history of untreated brain metastasis or history of leptomeningeal disease or spinal cord compression

• Has failed to recover from the reversible effects of prior anticancer therapy (does not apply to GBM cohort)

• Has uncontrolled or poorly controlled hypertension

• Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease

• Has had any major cardiovascular event within 6 months prior to study drug administration

• Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results

• Has had major surgery within 4 weeks before first study drug administration

• Has known HIV

• Has an active infection requiring systemic treatment

• Is participating in another therapeutic clinical trial

Additional Excusion Criteria for GBM cohort:

• Has received prior anti-VEGF therapy including bevacizumab (i.e. patients must be bevacizumab naïve)

• Is receiving enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of belzutifan

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Solid Tumors
• Carcinoma
• Carcinoma, Renal Cell
• ccRCC
• Clear Cell Renal Cell Carcinoma
• GBM
• Glioblastoma
• Glioblastoma Multiforme
• Glioblastoma, Adult
• Kidney Cancer
• Neoplasms
• RCC
• RCC, Clear Cell Adenocarcinoma
• Renal Cell Carcinoma Recurrent
• Renal Cell Carcinoma, Clear Cell Adenocarcinoma
• Renal Cell Carcinoma, Metastatic
• Solid Carcinoma
• Solid Tumor
• Solid Tumor, Adult

Intervention

Drug:
• Belzutifan
Belzutifan is a highly selective small molecule that inhibits the function of the HIF-2a transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peloton Therapeutics, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose (MTD)	21-Day Dose Limiting Toxicity Observation Period per Dose Group	3 Weeks

External Links

•   Merck Oncology Clinical Trials Information