A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)
- Conditions
- Renal Cell Carcinoma (RCC)Clear Cell Renal Cell Carcinoma (ccRCC)Kidney CancerRenal CancerRenal Cell CarcinomaRenal Cell Cancer MetastaticRenal Cell Carcinoma RecurrentRenal Cell Cancer, RecurrentKidney
- Interventions
- Registration Number
- NCT03634540
- Lead Sponsor
- Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 118
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Has locally advanced or metastatic RCC with predominantly clear cell subtype
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Has at least one measurable lesion as defined by RECIST version 1.1
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
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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
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Cohort 2: Participants must have received prior immunotherapy and no more than two prior treatments for advanced or metastatic ccRCC
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1) Cabozantinib Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time. Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2) Cabozantinib Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time. Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1) Belzutifan Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time. Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2) Belzutifan Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) 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
Name Time Method Progression Free Survival (PFS) 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.
Number of participants discontinuing study treatment due to an Adverse Event (AE) 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.
Belzutifan Plasma Concentration 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.
Belzutifan Metabolite Plasma Concentration 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.
Cabozantinib Plasma Concentration 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.
Duration of Response (DOR) 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).
Overall Survival (OS) 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.
Number of participants experiencing an Adverse Event (AE) 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.
Time to Response (TTR) 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.
Trial Locations
- Locations (10)
Tennessee Oncology, PLLC ( Site 0024)
🇺🇸Chattanooga, Tennessee, United States
Swedish Cancer Institute ( Site 0018)
🇺🇸Seattle, Washington, United States
Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035)
🇺🇸Seattle, Washington, United States
Dana Farber Cancer Center ( Site 0006)
🇺🇸Boston, Massachusetts, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010)
🇺🇸Dallas, Texas, United States
Sylvester Comprehensive Cancer Center ( Site 0023)
🇺🇸Miami, Florida, United States
Tennessee Oncology, PLLC ( Site 0001)
🇺🇸Nashville, Tennessee, United States
Karmanos Cancer Institute ( Site 0033)
🇺🇸Detroit, Michigan, United States
USC Norris Comprehensive Cancer Center ( Site 0060)
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003)
🇺🇸Los Angeles, California, United States