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)

• ClinicalTrials.gov Identifier: NCT05468697
• Recruitment Status: Recruiting
• First Posted: July 21, 2022
• Last Update Posted: February 2, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: July 18, 2022
• First Posted Date: July 21, 2022
• Last Update Posted Date: February 2, 2024
• Actual Study Start Date: August 10, 2022
• Estimated Primary Completion Date: March 16, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2022)

• Part 1 - Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT) [ Time Frame: 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) [ Time Frame: Up to approximately 4.5 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 [ Time Frame: Up to approximately 4.5 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 [ Time Frame: Up to approximately 4.5 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 18, 2022)

• Part 2 - Clinical Benefit Rate (CBR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator [ Time Frame: Up to approximately 4.5 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 [ Time Frame: Up to approximately 4.5 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 [ Time Frame: Up to approximately 4.5 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) [ Time Frame: Up to approximately 4.5 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) [ Time Frame: Up to approximately 4.5 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 [ Time Frame: Up to approximately 4.5 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: A Multicenter, Open-label, Randomized, Phase 1/2 Study of Belzutifan in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Renal Cell Carcinoma

Intervention

• Drug: Belzutifan
  40 mg tablet administered orally at a dose of 120 mg.
  Other Names:

  • WELIREG™
  • MK-6482
  • PT2977
• Drug: Palbociclib
  75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.
  Other Names:

  • IBRANCE®
  • PD 0332991

Study Arms

• Experimental: Part 1 - Beltuzifan 120 mg + Palbociclib 75 mg
  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.
  Interventions:

  • Drug: Belzutifan
  • Drug: Palbociclib
• Experimental: Part 1 - Beltuzifan 120 mg + Palbociclib 100 mg
  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.
  Interventions:

  • Drug: Belzutifan
  • Drug: Palbociclib
• Experimental: Part 1 - Beltuzifan 120 mg + Palbociclib 125 mg
  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.
  Interventions:

  • Drug: Belzutifan
  • Drug: Palbociclib
• Experimental: Part 2 - Beltuzifan 120 mg + 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.
  Interventions:

  • Drug: Belzutifan
  • Drug: Palbociclib
• Experimental: Part 2 - Beltuzifan 120 mg
  Participants receive beltuzifan 120 mg orally QD until progressive disease or discontinuation.
  Intervention: Drug: Belzutifan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 18, 2022): 180
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 16, 2027
• Estimated Primary Completion Date: March 16, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Australia, Israel, United States

Administrative Information

• NCT Number: NCT05468697
• Other Study ID Numbers: 6482-024; MK-6482-024 ( Other Identifier: Merck ); LITESPARK-024 ( Other Identifier: Merck ); 2023-504963-17 ( Registry Identifier: EU CT )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: January 2024