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

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ClinicalTrials.gov Identifier: NCT03634540
Recruitment Status : Recruiting
First Posted : August 16, 2018
Last Update Posted : August 8, 2022
Sponsor:
Information provided by (Responsible Party):
Peloton Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
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 Drug: Belzutifan Drug: Cabozantinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Belzutifan in combination with cabozantinib administered orally once daily
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of PT2977 in Combination With Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : August 31, 2025
Estimated Study Completion Date : August 31, 2025


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:
  • PT2977, MK-6482
  • WELIREG™

Drug: Cabozantinib
Cabozantinib tablets administered orally.
Other Name: 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:
  • PT2977, MK-6482
  • WELIREG™

Drug: Cabozantinib
Cabozantinib tablets administered orally.
Other Name: CABOMETYX®




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03634540


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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United States, California
USC Norris Comprehensive Cancer Center ( Site 0060) Recruiting
Los Angeles, California, United States, 90033
Contact: Study Coordinator    323-865-3000      
Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003) Recruiting
Los Angeles, California, United States, 90048
Contact: Study Coordinator    310-248-6728      
United States, Florida
Sylvester Comprehensive Cancer Center ( Site 0023) Recruiting
Miami, Florida, United States, 33136
Contact: Study Coordinator    305-243-1287      
United States, Massachusetts
Dana Farber Cancer Center ( Site 0006) Recruiting
Boston, Massachusetts, United States, 02215
Contact: Study Coordinator    617-632-5456      
United States, Michigan
Karmanos Cancer Institute ( Site 0033) Recruiting
Detroit, Michigan, United States, 48201
Contact: Study Coordinator    313-576-8717      
United States, Tennessee
Tennessee Oncology, PLLC ( Site 0024) Recruiting
Chattanooga, Tennessee, United States, 37404
Contact: Study Coordinator    423-698-1844      
Tennessee Oncology, PLLC ( Site 0001) Recruiting
Nashville, Tennessee, United States, 37203
Contact: Study Coordinator    615-329-7274      
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010) Completed
Dallas, Texas, United States, 75246
United States, Washington
Swedish Cancer Institute ( Site 0018) Recruiting
Seattle, Washington, United States, 98104
Contact: Study Coordinator    USA 018 Principal Investigator      
Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035) Recruiting
Seattle, Washington, United States, 98109
Contact: Study Coordinator    206-606-7763      
Sponsors and Collaborators
Peloton Therapeutics, Inc.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
Additional Information:
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Responsible Party: Peloton Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03634540    
Other Study ID Numbers: 6482-003
PT2977-201 ( Other Identifier: Peloton )
MK-6482-003 ( Other Identifier: Merck )
First Posted: August 16, 2018    Key Record Dates
Last Update Posted: August 8, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peloton Therapeutics, Inc.:
hypoxia-inducible factor (HIF)
hypoxia-inducible factor 2 alpha (HIF-2α, HIF-2 alpha)
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases