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Renal Cell Carcinoma (RCC)Phase 2NCT03634540

A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)

A Phase 2 study testing Belzutifan and Cabozantinib in people with Renal Cell Carcinoma (RCC) and Clear Cell Renal Cell Carcinoma (ccRCC), run by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 10 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is an open-label Phase 2 study which will evaluate the efficacy and safety of belzutifan in combination with cabozantinib in participants with advanced ccRCC. Belzutifan and cabozantinib will be administered orally once daily. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Belzutifan and Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
118 participants
Where
10 sitesUnited States
Study dates
27 Sep 2018to 26 Feb 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 locally advanced or metastatic RCC with predominantly clear cell subtype
  • Has at least one measurable lesion as defined by RECIST version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Has adequate organ function defined as follows:
  • Absolute neutrophil count ≥ 1,000/µL, hemoglobin level ≥ 10 g/dL and platelet count ≥ 100,000/µL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at screening;
  • Serum creatinine level ≤ 2.0 × upper limit of normal (ULN)
  • Transaminase levels (AST/ALT) ≤ 3.0 × upper limit of normal (ULN); total bilirubin (TBILI) ≤ 1.5 mg/dL in the absence of Gilbert's disease *Cohort 1: Participants must not have received prior systemic therapy for advanced or metastatic ccRCC
  • Cohort 2: Participants must have received prior immunotherapy and no more than two prior treatments for advanced or metastatic ccRCC

Who cannot join

  • Has received prior treatment with belzutifan or other HIF2α inhibitors
  • Has received prior treatment with cabozantinib
  • Has had radiation therapy for bone metastases within two weeks of starting study drug
  • Has a history of untreated brain metastases or history of leptomeningeal disease or spinal cord compression
  • Has failed to recover from the reversible effects of prior anticancer therapy
  • Has uncontrolled or poorly controlled hypertension
Show all 12Show fewer
  • Is receiving anticoagulant therapy
  • 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 3 months before first study drug administration
  • Has an active infection requiring systemic treatment
  • Is participating in another therapeutic clinical trial

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Dana Farber Cancer Center ( Site 0006)

    Boston, Massachusetts, 02215

  • Tennessee Oncology, PLLC ( Site 0024)

    Chattanooga, Tennessee, 37404

  • Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010)

    Dallas, Texas, 75246

  • Karmanos Cancer Institute ( Site 0033)

    Detroit, Michigan, 48201

  • USC Norris Comprehensive Cancer Center ( Site 0060)

    Los Angeles, California, 90033

  • Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003)

    Los Angeles, California, 90048

  • Sylvester Comprehensive Cancer Center ( Site 0023)

    Miami, Florida, 33136

  • Tennessee Oncology, PLLC ( Site 0001)

    Nashville, Tennessee, 37203

  • Swedish Cancer Institute ( Site 0018)

    Seattle, Washington, 98104

  • Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035)

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase 2 Trial of PT2977 in Combination With Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma

This is an open-label Phase 2 study which will evaluate the efficacy and safety of belzutifan in combination with cabozantinib in participants with advanced ccRCC. Belzutifan and cabozantinib will be administered orally once daily.

Being tested
Belzutifan, Cabozantinib
Keywords
hypoxia-inducible factor (HIF), hypoxia-inducible factor 2 alpha (HIF-2α, HIF-2 alpha)
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelzutifanDrug

    Also called PT2977, MK-6482, WELIREG™

    Belzutifan tablets administered orally.

  • CabozantinibDrug

    Also called CABOMETYX®

    Cabozantinib tablets administered orally.

Study groups in NCT03634540
Study groupRoleWhat they receive
Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)ExperimentalNaïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.
Receives: Drug: Belzutifan; Drug: Cabozantinib
Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)ExperimentalParticipants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.
Receives: Drug: Belzutifan; Drug: Cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    ORR is defined as the percentage of participants with a best confirmed response of Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as determined by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

    Measured: Up to approximately 2 years

Secondary outcomes (9)

  1. Progression Free Survival (PFS)

    PFS is defined as the interval from the start of study treatment until the earlier of the first documentation of disease progression determined by RECIST 1.1 or death from any cause.

    Measured: Up to approximately 2 years

  2. Duration of Response (DOR)

    DOR is defined as the interval from the first documentation of response, as determined by RECIST 1.1, to the earlier of the first documentation of disease progression or death from any cause, and calculated for participants with a best confirmed response of CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions).

    Measured: Up to approximately 2 years

  3. Time to Response (TTR)

    TTR is defined as the interval from the start of study treatment to the first documentation of a response, as determined by RECIST 1.1, and calculated for participants with a best confirmed response of CR or PR.

    Measured: Up to approximately 2 years

  4. Overall Survival (OS)

    OS is defined as the interval from the start of treatment to the death of the participant from any cause.

    Measured: Up to approximately 2 years

  5. Number of participants experiencing an Adverse Event (AE)

    An AE is defined as any untoward medical occurrence in a participant regardless of its causal relationship to study treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not it is considered to be study drug related. Included in this definition are any newly occurring events and any previous condition that has increased in severity or frequency since the administration of study drug.

    Measured: Up to approximately 2 years

  6. Number of participants discontinuing study treatment due to an Adverse Event (AE)

    An AE is defined as any untoward medical occurrence in a participant regardless of its causal relationship to study treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not it is considered to be study drug related. Included in this definition are any newly occurring events and any previous condition that has increased in severity or frequency since the administration of study drug.

    Measured: Up to approximately 2 years

  7. Belzutifan Plasma Concentration

    Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.

    Measured: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose

  8. Belzutifan Metabolite Plasma Concentration

    Blood samples for the determination of belzutifan metabolite concentration will be collected at pre-specified timepoints before and after treatment administration.

    Measured: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose

  9. Cabozantinib Plasma Concentration

    Blood samples for the determination of cabozantinib concentration will be collected at pre-specified timepoints before and after treatment administration.

    Measured: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2018
  2. Study start27 Sep 2018
  3. Primary completion26 Feb 2027 (estimated)
  4. Study completion26 Feb 2027 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Belzutifan in combination with cabozantinib administered orally once daily
Masking
None (open label)
Enrolment
118 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03634540
Sponsor's protocol ID
6482-003
Other IDs
PT2977-201, MK-6482-003
Status last verified
Dec 2024
First submitted
3 Aug 2018
Last updated
20 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Choueiri TK, McDermott DF, Merchan J, Bauer TM, Figlin R, Heath EI, Michaelson MD, Arrowsmith E, D'Souza A, Zhao S, Roy A, Perini R, Vickery D, Tykodi SS. Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. Lancet Oncol. 2023 May;24(5):553-562. doi: 10.1016/S1470-2045(23)00097-9. Epub 2023 Mar 31.

    PubMed 37011650

  • Choueiri TK, Merchan JR, Figlin R, McDermott DF, Arrowsmith E, Michaelson MD, Tykodi SS, Heath EI, Spigel DR, D'Souza A, Kassalow L, Perini RF, Vickery D, Bauer TM. Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): an open-label, single-arm, phase 2 study. Lancet Oncol. 2025 Jan;26(1):64-73. doi: 10.1016/S1470-2045(24)00649-1.

    PubMed 39756444

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Belzutifan and Cabozantinib in people with Renal Cell Carcinoma (RCC) and Clear Cell Renal Cell Carcinoma (ccRCC), run by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to approximately 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03634540, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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