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

NCT03634540 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: 6482-003PT2977-201MK-6482-003
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Renal Cell Carcinoma (RCC); Clear Cell Renal Cell Carcinoma (ccRCC); Kidney Cancer; Renal Cancer; Renal Cell Carcinoma; Renal Cell Cancer Metastatic; Renal Cell Carcinoma Recurrent; Renal Cell Cancer, Recurrent; Kidney

Keywords

hypoxia-inducible factor (HIF); hypoxia-inducible factor 2 alpha (HIF-2α, HIF-2 alpha)

Outcome Measures

Primary Outcomes (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).

  Up to approximately 2 years

Secondary Outcomes (9)

• Progression Free Survival (PFS)

  Up to approximately 2 years

• Duration of Response (DOR)

  Up to approximately 2 years

• Time to Response (TTR)

  Up to approximately 2 years

• Overall Survival (OS)

  Up to approximately 2 years

• Number of participants experiencing an Adverse Event (AE)

  Up to approximately 2 years

Study Arms (2)

Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)

EXPERIMENTAL

Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.

Drug: Belzutifan; Drug: Cabozantinib

Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)

EXPERIMENTAL

Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.

Drug: Belzutifan; Drug: Cabozantinib

Interventions

Belzutifan DRUG

Belzutifan tablets administered orally.

Also known as: PT2977, MK-6482, WELIREG™

Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2); Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)

Cabozantinib DRUG

Cabozantinib tablets administered orally.

Also known as: CABOMETYX®

Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2); Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (10)

USC Norris Comprehensive Cancer Center ( Site 0060)

Los Angeles, California, 90033, United States

Location

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

Los Angeles, California, 90048, United States

Location

Sylvester Comprehensive Cancer Center ( Site 0023)

Miami, Florida, 33136, United States

Location

Dana Farber Cancer Center ( Site 0006)

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute ( Site 0033)

Detroit, Michigan, 48201, United States

Location

Tennessee Oncology, PLLC ( Site 0024)

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC ( Site 0001)

Nashville, Tennessee, 37203, United States

Location

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

Dallas, Texas, 75246, United States

Location

Swedish Cancer Institute ( Site 0018)

Seattle, Washington, 98104, United States

Location

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

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• 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.

  PMID: 37011650 RESULT

• 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.

  PMID: 39756444 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Recurrence

Interventions

belzutifan; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Belzutifan in combination with cabozantinib administered orally once daily

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 16, 2018
• Study Start: September 27, 2018
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 26, 2027
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

US (10)