Advanced Solid TumorsPhase 1NCT02974738
A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001)
A Phase 1 study testing Belzutifan in people with Advanced Solid Tumors and Solid Tumor, run by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Solid Tumor, Solid Carcinoma
- What is being tested?
- Belzutifan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- 7 Dec 2016to 8 Oct 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
About this study
Official title: A Phase 1, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors
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
Read the detailed 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)
- Conditions
- Advanced Solid Tumors, Solid Tumor, Solid Carcinoma, Solid Tumor, Adult, ccRCC, RCC, Clear Cell Adenocarcinoma
- Being tested
- Belzutifan
- Medical subject headings
- Carcinoma, Renal Cell, Kidney Neoplasms, Neoplasm Metastasis, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelzutifanDrug
Also called PT2977 Tablets, PT-2977, HIF-2α inhibitor, MK-6482, WELIREG™
Belzutifan is a highly selective small molecule that inhibits the function of the HIF-2α transcription factor. As a result, hypoxic signaling in cancer cells is impaired, blocking the transcription of several genes involved in oncogenesis
| Study group | Role | What they receive |
|---|---|---|
| Part 1A | Experimental | Drug: PART 1A: Belzutifan for the treatment of advanced solid tumors
Belzutifan inhibits HIF-2α and is a novel approach to treatment of solid tumors. Receives: Drug: Belzutifan |
| Part 1B | Experimental | Drug: PART 1B: Belzutifan for the treatment of advanced ccRCC
Belzutifan inhibits HIF-2α and is a novel approach to treatment of ccRCC. Receives: Drug: Belzutifan |
| Part 2 | Experimental | Drug: Part 2: Belzutifan for the treatment of other specified solid tumors
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors. Receives: Drug: Belzutifan |
| Part 2A | Experimental | Drug: Part 2A: Belzutifan for the treatment of patients with recurrent GBM who have been previously treated with radiation therapy and temozolomide
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors. Receives: Drug: Belzutifan |
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum tolerated dose (MTD)
21-Day Dose Limiting Toxicity Observation Period per Dose Group
Measured: 3 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2016 (estimated)
- Study start7 Dec 2016
- Primary completion12 Jan 2018
- Study completion8 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02974738
- Sponsor's protocol ID
- 6482-001
- Other IDs
- PT2977-101, MK-6482-001
- Status last verified
- Sep 2026
- First submitted
- 23 Nov 2016
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Jonasch E, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Dror Michaelson M, Appleman LJ, Roy A, Perini RF, Liu Y, Choueiri TK. Phase I LITESPARK-001 study of belzutifan for advanced solid tumors: Extended 41-month follow-up in the clear cell renal cell carcinoma cohort. Eur J Cancer. 2024 Jan;196:113434. doi: 10.1016/j.ejca.2023.113434. Epub 2023 Nov 15.
PubMed 38008031Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Michaelson MD, Appleman LJ, Thamake S, Perini RF, Zojwalla NJ, Jonasch E. Inhibition of hypoxia-inducible factor-2alpha in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021 May;27(5):802-805. doi: 10.1038/s41591-021-01324-7. Epub 2021 Apr 22.
PubMed 33888901