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

Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03634540
• Other study ID #: 6482-003
• Secondary ID: PT2977-201MK-648
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 27, 2018
• Est. completion date: August 31, 2025

Study information

• Verified date: May 2023
• Source: Peloton Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 118
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Has received prior treatment with belzutifan or other HIF2a 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma (ccRCC)
• Kidney
• Kidney Cancer
• Kidney Neoplasms
• Recurrence
• Renal Cancer
• Renal Cell Cancer Metastatic
• Renal Cell Cancer, Recurrent
• Renal Cell Carcinoma
• Renal Cell Carcinoma (RCC)
• Renal Cell Carcinoma Recurrent

Intervention

Drug:
• Belzutifan
Belzutifan tablets administered orally.
• Cabozantinib
Cabozantinib tablets administered orally.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Center ( Site 0006)	Boston	Massachusetts
United States	Tennessee Oncology, PLLC ( Site 0024)	Chattanooga	Tennessee
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010)	Dallas	Texas
United States	Karmanos Cancer Institute ( Site 0033)	Detroit	Michigan
United States	Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003)	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center ( Site 0060)	Los Angeles	California
United States	Sylvester Comprehensive Cancer Center ( Site 0023)	Miami	Florida
United States	Tennessee Oncology, PLLC ( Site 0001)	Nashville	Tennessee
United States	Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035)	Seattle	Washington
United States	Swedish Cancer Institute ( Site 0018)	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Peloton Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 t — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to approximately 2 years
Secondary	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).	Up to approximately 2 years
Secondary	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.	Up to approximately 2 years
Secondary	Overall Survival (OS)	OS is defined as the interval from the start of treatment to the death of the participant from any cause.	Up to approximately 2 years
Secondary	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.	Up to approximately 2 years
Secondary	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.	Up to approximately 2 years
Secondary	Belzutifan Plasma Concentration	Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.	Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
Secondary	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.	Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
Secondary	Cabozantinib Plasma Concentration	Blood samples for the determination of cabozantinib concentration will be collected at pre-specified timepoints before and after treatment administration.	Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose

External Links

•   Merck Oncology Clinical Trials Information