Back to resultsA Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)
Primary Purpose
Renal Cell Carcinoma (RCC), Clear Cell Renal Cell Carcinoma (ccRCC), Kidney Cancer
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Belzutifan
Cabozantinib
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma (RCC) focused on measuring hypoxia-inducible factor (HIF), hypoxia-inducible factor 2 alpha (HIF-2α, HIF-2 alpha)
Eligibility 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
Sites / Locations
- USC Norris Comprehensive Cancer Center ( Site 0060)
- Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003)
- Sylvester Comprehensive Cancer Center ( Site 0023)
- Dana Farber Cancer Center ( Site 0006)
- Karmanos Cancer Institute ( Site 0033)
- Tennessee Oncology, PLLC ( Site 0024)
- Tennessee Oncology, PLLC ( Site 0001)
- Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010)
- Swedish Cancer Institute ( Site 0018)
- Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)
Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)
Arm Description
Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.
Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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).
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.
Overall Survival (OS)
OS is defined as the interval from the start of treatment to the death of the participant from any cause.
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.
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.
Belzutifan Plasma Concentration
Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.
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.
Cabozantinib Plasma Concentration
Blood samples for the determination of cabozantinib concentration will be collected at pre-specified timepoints before and after treatment administration.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03634540
Brief Title
A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)
Official Title
A Phase 2 Trial of PT2977 in Combination With Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 27, 2018 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peloton Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Belzutifan in combination with cabozantinib administered orally once daily
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
118 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)
Arm Type
Experimental
Arm Description
Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.
Arm Title
Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)
Arm Type
Experimental
Arm Description
Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.
Intervention Type
Drug
Intervention Name(s)
Belzutifan
Other Intervention Name(s)
PT2977, MK-6482, WELIREG™
Intervention Description
Belzutifan tablets administered orally.
Intervention Type
Drug
Intervention Name(s)
Cabozantinib
Other Intervention Name(s)
CABOMETYX®
Intervention Description
Cabozantinib tablets administered orally.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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).
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Up to approximately 2 years
Title
Duration of Response (DOR)
Description
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).
Time Frame
Up to approximately 2 years
Title
Time to Response (TTR)
Description
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.
Time Frame
Up to approximately 2 years
Title
Overall Survival (OS)
Description
OS is defined as the interval from the start of treatment to the death of the participant from any cause.
Time Frame
Up to approximately 2 years
Title
Number of participants experiencing an Adverse Event (AE)
Description
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.
Time Frame
Up to approximately 2 years
Title
Number of participants discontinuing study treatment due to an Adverse Event (AE)
Description
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.
Time Frame
Up to approximately 2 years
Title
Belzutifan Plasma Concentration
Description
Blood samples for the determination of belzutifan concentration will be collected at pre-specified timepoints before and after treatment administration.
Time Frame
Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
Title
Belzutifan Metabolite Plasma Concentration
Description
Blood samples for the determination of belzutifan metabolite concentration will be collected at pre-specified timepoints before and after treatment administration.
Time Frame
Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
Title
Cabozantinib Plasma Concentration
Description
Blood samples for the determination of cabozantinib concentration will be collected at pre-specified timepoints before and after treatment administration.
Time Frame
Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
USC Norris Comprehensive Cancer Center ( Site 0060)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Sylvester Comprehensive Cancer Center ( Site 0023)
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Dana Farber Cancer Center ( Site 0006)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Cancer Institute ( Site 0033)
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Tennessee Oncology, PLLC ( Site 0024)
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Tennessee Oncology, PLLC ( Site 0001)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Swedish Cancer Institute ( Site 0018)
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035)
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
37011650
Citation
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.
Results Reference
result
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information
Learn more about this trial
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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