Back to results

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)

Primary Purpose

Renal Cell Carcinoma

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Belzutifan

Palbociclib

About this trial

This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Georgetown University Medical Center ( Site 1002)Recruiting
Beth Israel Deaconess Medical Center-Cancer Clinical Trials Office ( Site 1001)Recruiting
Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 1004)Recruiting
Macquarie University-MQ Health Clinical Trials Unit ( Site 2001)Recruiting
Rambam Health Care Campus-Oncology ( Site 3000)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Part 1 - Beltuzifan 120 mg + Palbociclib 75 mg

Part 1 - Beltuzifan 120 mg + Palbociclib 100 mg

Part 1 - Beltuzifan 120 mg + Palbociclib 125 mg

Part 2 - Beltuzifan 120 mg + Palbociclib

Part 2 - Beltuzifan 120 mg

Arm Description

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.

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.

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.

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.

Participants receive beltuzifan 120 mg orally QD until progressive disease or discontinuation.

Outcomes

Primary Outcome Measures

Part 1 - Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)

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)

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

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

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

Part 2 - Clinical Benefit Rate (CBR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

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

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

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)

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)

Part 2 - Number of Participants Who Discontinue Study Treatment Due to an AE

Full Information

NCT ID

NCT05468697

First Posted

July 18, 2022

Last Updated

September 6, 2023

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT05468697

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 10, 2022 (Actual)

Primary Completion Date

March 16, 2027 (Anticipated)

Study Completion Date

March 16, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1 - Beltuzifan 120 mg + Palbociclib 75 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 1 - Beltuzifan 120 mg + Palbociclib 100 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 1 - Beltuzifan 120 mg + Palbociclib 125 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2 - Beltuzifan 120 mg + Palbociclib

Arm Type

Experimental

Arm Description

Arm Title

Part 2 - Beltuzifan 120 mg

Arm Type

Experimental

Arm Description

Participants receive beltuzifan 120 mg orally QD until progressive disease or discontinuation.

Intervention Type

Drug

Intervention Name(s)

Belzutifan

Other Intervention Name(s)

WELIREG™, MK-6482, PT2977

Intervention Description

40 mg tablet administered orally at a dose of 120 mg.

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Other Intervention Name(s)

IBRANCE®, PD 0332991

Intervention Description

75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.

Primary Outcome Measure Information:

Title

Part 1 - Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)

Description

Time Frame

Up to approximately 28 days

Title

Part 1 - Number of Participants Who Experience at Least One Adverse Event (AE)

Description

Time Frame

Up to approximately 4.5 years

Title

Part 1 - Number of Participants Who Discontinue Study Treatment Due to an AE

Description

Time Frame

Up to approximately 4.5 years

Title

Part 2 - Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

Description

Time Frame

Up to approximately 4.5 years

Secondary Outcome Measure Information:

Title

Part 2 - Clinical Benefit Rate (CBR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

Description

Time Frame

Up to approximately 4.5 years

Title

Part 2 - Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

Description

Time Frame

Up to approximately 4.5 years

Title

Part 2 - Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

Description

Time Frame

Up to approximately 4.5 years

Title

Part 2 - Overall Survival (OS)

Description

OS is defined as the time from randomization to death due to any cause. OS will be reported for Part 2.

Time Frame

Up to approximately 4.5 years

Title

Part 2 - Number of Participants Who Experience at Least One Adverse Event (AE)

Description

Time Frame

Up to approximately 4.5 years

Title

Part 2 - Number of Participants Who Discontinue Study Treatment Due to an AE

Description

Time Frame

Up to approximately 4.5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Toll Free Number

Phone

1-888-577-8839

Trialsites@merck.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

Facility Information:

Facility Name

Georgetown University Medical Center ( Site 1002)

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

617-797-5460

Facility Name

Beth Israel Deaconess Medical Center-Cancer Clinical Trials Office ( Site 1001)

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

617-632-9250

Facility Name

Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 1004)

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84112

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

801-414-1779

Facility Name

Macquarie University-MQ Health Clinical Trials Unit ( Site 2001)

City

Macquarie University

State/Province

New South Wales

ZIP/Postal Code

2109

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

+61298122956

Facility Name

Rambam Health Care Campus-Oncology ( Site 3000)

City

Haifa

ZIP/Postal Code

3109601

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

+972-4-7776400

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Links:

URL

https://www.merckclinicaltrials.com/

Description

Merck Clinical Trials Information

Learn more about this trial

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)

We'll reach out to this number within 24 hrs