A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6482-024/LITESPARK-024)
- Registration Number
- NCT05468697
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of belzutifan monotherapy and belzutifan plus palbociclib combination therapy in participants with advanced clear-cell renal cell carcinoma (ccRCC) who experienced disease progression on or after receiving prior therapy. Part 1 will establish the safety of belzutifan plus palbociclib and determine a recommended dosage of palbociclib for the combination therapy by ascending dose escalation. Part 2 will evaluate the efficacy and safety of belzutifan plus palbociclib at the dosage level determined in Part 1.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
- Has a histologically confirmed diagnosis of unresectable Stage IV (per American Joint Committee on Cancer [AJCC], 8th Edition) RCC with clear-cell component
- Has had disease progression on or after having received at least 2 systemic treatments for unresectable Stage IV RCC with prior anti-programmed cell death 1 ligand 1 (PD-1/L1) and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination
- Has measurable disease per RECIST 1.1 as assessed by the investigator and verified by blinded independent central review (BICR)
- Has recovered from all AEs due to previous therapies
- Has hypoxia, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has clinically significant cardiac disease
- Has moderate to severe hepatic impairment
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
- Has received prior treatment of belzutifan or palbociclib
- Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
- Has had major surgery ≤3 weeks prior to first dose of study intervention
- Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 - Beltuzifan 120 mg Belzutifan Participants receive beltuzifan 120 mg orally QD until progressive disease or discontinuation. Part 1 - Beltuzifan 120 mg + Palbociclib 75 mg Palbociclib Participants receive beltuzifan 120 mg orally once per day (QD) and palbociclib 75 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Part 1 - Beltuzifan 120 mg + Palbociclib 100 mg Palbociclib Participants receive beltuzifan 120 mg orally QD and palbociclib 100 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Part 1 - Beltuzifan 120 mg + Palbociclib 125 mg Palbociclib Participants receive beltuzifan 120 mg orally QD and palbociclib 125 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Part 1 - Beltuzifan 120 mg + Palbociclib 125 mg Belzutifan Participants receive beltuzifan 120 mg orally QD and palbociclib 125 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Part 2 - Beltuzifan 120 mg + Palbociclib Belzutifan Participants receive beltuzifan 120 mg orally QD and palbociclib orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Palbociclib will be administered at a dosage level determined in Part 1. Part 2 - Beltuzifan 120 mg + Palbociclib Palbociclib Participants receive beltuzifan 120 mg orally QD and palbociclib orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Palbociclib will be administered at a dosage level determined in Part 1. Part 1 - Beltuzifan 120 mg + Palbociclib 75 mg Belzutifan Participants receive beltuzifan 120 mg orally once per day (QD) and palbociclib 75 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Part 1 - Beltuzifan 120 mg + Palbociclib 100 mg Belzutifan Participants receive beltuzifan 120 mg orally QD and palbociclib 100 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
- Primary Outcome Measures
Name Time Method Part 1 - Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT) Up to approximately 28 days A DLT consists of one or more of the following toxicities: Grade (Gr) 3 or 4 hypoxia or dyspnea; Gr 3 or 4 nausea, vomiting, or diarrhea if persistent for \>48 hours despite therapy; Gr 3 or 4 cardiovascular, vascular, or thrombotic events; Nonhematologic AE ≥Gr 3 in severity with exceptions; Gr 3 rash that does not resolve within 2 weeks; Gr 3 nonhematologic toxicity if persisting despite optimal medical treatment; Gr 3 or 4 hematologic toxicities; Gr 3 or 4 febrile neutropenia; Gr 3 or 4 nonhematologic laboratory value; Any aspartate aminotransferase or alanine aminotransferase \>8x the upper limit of normal (ULN) or 5 to 8x ULN persisting for \>2 weeks; \>2 weeks delay in dosing due to intervention-related toxicity; Intervention-related toxicity causing intervention discontinuation in the first 28 days of dosing; Missing \>20% of intervention doses due to drug-related AEs; Gr 5 toxicity. The number of participants who experience at least one DLT will be reported for Part 1.
Part 1 - Number of Participants Who Experience at Least One Adverse Event (AE) Up to approximately 6 years An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be reported for Part 1.
Part 1 - Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 6 years An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. The number of participants who discontinued from the study treatment due to an AE will be reported for Part 1.
Part 2 - Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Up to approximately 6 years ORR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by the investigator based on RECIST 1.1 will be presented for Part 2.
- Secondary Outcome Measures
Name Time Method Part 2 - Clinical Benefit Rate (CBR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Up to approximately 6 years CBR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD: Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study) for ≥6 months per RECIST 1.1. The percentage of participants with CBR will be presented for Part 2.
Part 2 - Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Up to approximately 6 years For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by the investigator will be presented for Part 2.
Part 2 - Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Up to approximately 6 years 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 the investigator will be presented for Part 2.
Part 2 - Overall Survival (OS) Up to approximately 6 years OS is defined as the time from randomization to death due to any cause. OS will be reported for Part 2.
Part 2 - Number of Participants Who Experience at Least One Adverse Event (AE) Up to approximately 6 years An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be reported for Part 2.
Part 2 - Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 6 years An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. The number of participants who discontinued from the study treatment due to an AE will be reported for Part 2.
Trial Locations
- Locations (13)
Georgetown University Medical Center ( Site 1002)
🇺🇸Washington, District of Columbia, United States
University of Chicago Medical Center ( Site 1007)
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Medical Center-Cancer Clinical Trials Office ( Site 1001)
🇺🇸Boston, Massachusetts, United States
Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 1004)
🇺🇸Salt Lake City, Utah, United States
Macquarie University-MQ Health Clinical Trials Unit ( Site 2001)
🇦🇺Macquarie University, New South Wales, Australia
Westmead Hospital ( Site 2006)
🇦🇺Westmead, New South Wales, Australia
Frankston Hospital-Oncology and Haematology ( Site 2005)
🇦🇺Frankston, Victoria, Australia
One Clinical Research ( Site 2008)
🇦🇺Nedlands, Western Australia, Australia
Emek Medical Center-oncology ( Site 3003)
🇮🇱Afula, Israel
Rambam Health Care Campus-Oncology ( Site 3000)
🇮🇱Haifa, Israel
Shaare Zedek Medical Center-Oncology ( Site 3002)
🇮🇱Jerusalem, Israel
Rabin Medical Center-Oncology ( Site 3004)
🇮🇱Petah Tikva, Israel
Sourasky Medical Center ( Site 3005)
🇮🇱Tel Aviv, Israel