Clinical trial NCT05468697: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Programmed cell death ligand 1 (PD-L1)
Hypoxia inducible factor 2 alpha (HIF-2 alpha)
Hypoxia inducible factor 2α (HIF-2α)
Renal Cell Carcinoma (RCC)
Kidney Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-07-21
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part 1 - Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
timeFrame: Up to approximately 28 days
measure: Part 1 - Number of Participants Who Experience at Least One Adverse Event (AE)
timeFrame: Up to approximately 6 years
measure: Part 1 - Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 6 years
measure: Part 2 - Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
timeFrame: Up to approximately 6 years
Secondary outcomes:
measure: Part 2 - Clinical Benefit Rate (CBR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
timeFrame: Up to approximately 6 years
measure: Part 2 - Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
timeFrame: Up to approximately 6 years
measure: Part 2 - Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
timeFrame: Up to approximately 6 years
measure: Part 2 - Overall Survival (OS)
timeFrame: Up to approximately 6 years
measure: Part 2 - Number of Participants Who Experience at Least One Adverse Event (AE)
timeFrame: Up to approximately 6 years
measure: Part 2 - Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 6 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Medical Center ( Site 1002)
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Medical Center ( Site 1007)
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center-Cancer Clinical Trials Office ( Site 1001)
state: Massachusetts
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 1004)
state: Utah
city: Macquarie University
country: Australia
facility: Macquarie University-MQ Health Clinical Trials Unit ( Site 2001)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 2006)
state: New South Wales
city: Frankston
country: Australia
facility: Frankston Hospital-Oncology and Haematology ( Site 2005)
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research ( Site 2008)
state: Western Australia
city: Afula
country: Israel
facility: Emek Medical Center-oncology ( Site 3003)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 3000)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center-Oncology ( Site 3002)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center-Oncology ( Site 3004)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 3005)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: