Clinical trial NCT03634540: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 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)
Lead sponsor: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2018-08-16
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Belzutifan in combination with cabozantinib administered orally once daily
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Time to Response (TTR)
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Number of participants experiencing an Adverse Event (AE)
timeFrame: Up to approximately 2 years
measure: Number of participants discontinuing study treatment due to an Adverse Event (AE)
timeFrame: Up to approximately 2 years
measure: Belzutifan Plasma Concentration
timeFrame: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
measure: Belzutifan Metabolite Plasma Concentration
timeFrame: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
measure: Cabozantinib Plasma Concentration
timeFrame: Weeks 1 and 4: pre-dose, 2 and 6 hours post-dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center ( Site 0060)
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0003)
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center ( Site 0023)
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Center ( Site 0006)
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute ( Site 0033)
state: Michigan
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC ( Site 0024)
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC ( Site 0001)
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 0010)
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute ( Site 0018)
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0035)
state: Washington
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.