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

May 2, 2023 updated by: Peloton Therapeutics, Inc.

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

118

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC Norris Comprehensive Cancer Center ( Site 0060)
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003)
    • Florida
      • Miami, Florida, United States, 33136
        • Sylvester Comprehensive Cancer Center ( Site 0023)
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Center ( Site 0006)
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute ( Site 0033)
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology, PLLC ( Site 0024)
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC ( Site 0001)
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010)
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute ( Site 0018)
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)
Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.
Drug: Belzutifan
Belzutifan tablets administered orally.
Other Names:
  • WELIREG™
  • PT2977, MK-6482
Drug: Cabozantinib
Cabozantinib tablets administered orally.
Other Names:
  • CABOMETYX®
Experimental: Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)
Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.
Drug: Belzutifan
Belzutifan tablets administered orally.
Other Names:
  • WELIREG™
  • PT2977, MK-6482
Drug: Cabozantinib
Cabozantinib tablets administered orally.
Other Names:
  • CABOMETYX®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Up to approximately 2 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Up to approximately 2 years
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
Duration of Response (DOR)
Time Frame: Up to approximately 2 years
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
Time to Response (TTR)
Time Frame: Up to approximately 2 years
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
Overall Survival (OS)
Time Frame: Up to approximately 2 years
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
Number of participants experiencing an Adverse Event (AE)
Time Frame: Up to approximately 2 years
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
Number of participants discontinuing study treatment due to an Adverse Event (AE)
Time Frame: Up to approximately 2 years
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
Belzutifan Plasma Concentration
Time Frame: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
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
Belzutifan Metabolite Plasma Concentration
Time Frame: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
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
Cabozantinib Plasma Concentration
Time Frame: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peloton Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 27, 2018

Primary Completion (Anticipated)

August 31, 2025

Study Completion (Anticipated)

August 31, 2025

Study Registration Dates

First Submitted

August 3, 2018

First Submitted That Met QC Criteria

August 14, 2018

First Posted (Actual)

August 16, 2018

Study Record Updates

Last Update Posted (Estimate)

May 4, 2023

Last Update Submitted That Met QC Criteria

May 2, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-003
  • PT2977-201 (Other Identifier: Peloton)
  • MK-6482-003 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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