Active, not recruiting
Phase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Condition(s) studied
Carcinoma, Renal Cell
Investigational drug(s) / intervention(s)
BelzutifanLenvatinibCabozantinib
Belzutifan: Immediate-release 40 mg tablet
Lenvatinib: Capsule available in 4 mg and 10 mg dosages
Cabozantinib: Tablet available in 20 mg, 40 mg and 60 mg dosages
Study summary
This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.
The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.
Eligibility
Inclusion Criteria:
* Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
* Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.
* Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
* Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
* Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
* Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC.
* A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
* A female participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
* Adequately controlled blood pressure.
* Adequate organ function.
Exclusion Criteria:
* A pulse oximeter reading \<92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
* Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
* Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Clinically significant cardiac disease within 6 months of first dose of study intervention.
* Prolongation of QTc interval to \>480 ms.
* Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
* Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
* Moderate to severe hepatic impairment.
* History of significant bleeding within 3 months before randomization.
* History of solid organ transplantation.
* Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
* Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
* Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
* Received colony-stimulating factors \[eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)\] within 28 days before randomization.
* Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
* Prior treatment with lenvatinib.
* Prior treatment with cabozantinib.
* Currently participating in a study of an investigational agent or using an investigational device.
* Active infection requiring systemic therapy.
* History of human immunodeficiency virus (HIV) infection.
* History of hepatitis B or known active hepatitis C infection.
Primary outcome measure(s)
- Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) — Up to approximately 34 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented.
- Overall Survival (OS) — Up to approximately 44 months
OS is defined as time from randomization to death due to any cause.
Trial sites (184)
| Facility | City | Region | Status |
| Ironwood Cancer & Research Centers ( Site 0077) |
Chandler |
Arizona |
|
| Cedars Sinai Medical Center ( Site 0027) |
Los Angeles |
California |
|
| UCLA Hematology/Oncology - Santa Monica ( Site 0048) |
Los Angeles |
California |
|
| St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0095) |
Orange |
California |
|
| University of California, Irvine ( Site 0029) |
Orange |
California |
|
| Providence Saint John's Health Center ( Site 0083) |
Santa Monica |
California |
|
| Georgetown University Medical Center ( Site 0006) |
Washington D.C. |
District of Columbia |
|
| AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0003) |
Orlando |
Florida |
|
| Orlando Health, Inc. ( Site 0035) |
Orlando |
Florida |
|
| University Cancer & Blood Center, LLC ( Site 0057) |
Athens |
Georgia |
|
| Emory University Hospital ( Site 0012) |
Atlanta |
Georgia |
|
| Rush University Medical Center ( Site 0040) |
Chicago |
Illinois |
|
| Illinois Cancer Care, PC ( Site 0008) |
Peoria |
Illinois |
|
| Parkview Cancer Institute ( Site 0088) |
Fort Wayne |
Indiana |
|
| Norton Cancer Institute - St. Matthews ( Site 0065) |
Louisville |
Kentucky |
|
| Tulane University School of Medicine ( Site 0098) |
New Orleans |
Louisiana |
|
| Lahey Hospital & Medical Center ( Site 0090) |
Burlington |
Massachusetts |
|
| Cancer & Hematology Centers of Western Michigan ( Site 0018) |
Grand Rapids |
Michigan |
|
| HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0005) |
Saint Louis Park |
Minnesota |
|
| University of Mississippi Medical Ctr ( Site 0037) |
Jackson |
Mississippi |
|
| Cancer Partners of Nebraska ( Site 0086) |
Lincoln |
Nebraska |
|
| Rutgers Cancer Institute of New Jersey ( Site 0078) |
New Brunswick |
New Jersey |
|
| R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013) |
Lake Success |
New York |
|
| Memorial Sloan Kettering Cancer Center ( Site 0055) |
New York |
New York |
|
| Levine Cancer Institute ( Site 0004) |
Charlotte |
North Carolina |
|
| Duke Cancer Institute ( Site 0096) |
Durham |
North Carolina |
|
| Lehigh Valley Hospital- Cedar Crest-Oncology Clinical Trials ( Site 0056) |
Allentown |
Pennsylvania |
|
| University of Texas, Southwestern Medical Center ( Site 0015) |
Dallas |
Texas |
|
| Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 7001) |
Salt Lake City |
Utah |
|
| University of Vermont Medical Center ( Site 0001) |
Burlington |
Vermont |
|
| Blue Ridge Cancer Care - Roanoke ( Site 0043) |
Roanoke |
Virginia |
|
| Seattle Cancer Care Alliance-Renal/Melanoma/MCC ( Site 0093) |
Seattle |
Washington |
|
| Central Washington Health Services Association d/b/a Confluence Health ( Site 0061) |
Wenatchee |
Washington |
|
| Centro de Urología (CDU) ( Site 0803) |
CABA |
Buenos Aires |
|
| Hospital Británico de Buenos Aires-Oncology ( Site 0801) |
Ciudad Autónoma de Buenos Aires |
Buenos Aires |
|
| Instituto Alexander Fleming ( Site 0800) |
Ciudad Autónoma de Buenos Aires |
Buenos Aires |
|
| Asociación de Beneficencia Hospital Sirio Libanés ( Site 0804) |
Buenos Aires |
Buenos Aires F.D. |
|
| Sanatorio Británico-Clinical Oncology Department ( Site 0802) |
Rosario |
Santa Fe Province |
|
| Sanatorio Parque ( Site 0806) |
Rosario |
Santa Fe Province |
|
| GenesisCare North Shore ( Site 4011) |
St Leonards |
New South Wales |
|
+ 144 more sites — see the full list on the official registry below.