Phase 1/2 Study of Belzutifan Plus Palbociclib Versus Belzutifan in Advanced Renal Cell Carcinoma (RCC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 13 Jun 2025

Decision date (initial)

2024-07-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504963-17-00

WHO UTN

U1111-1290-4845

ClinicalTrials.gov

NCT05468697

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Dose response, Efficacy, Safety

1. Part 1: To assess the safety and tolerability, and to establish the recommended Phase 2 dose (RP2D) of belzutifan plus palbociclib
2. Part 2: To evaluate the objective response rate (ORR) as assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in each arm

Secondary objectives 5

1. Part 2: To evaluate the clinical benefit rate (CBR) as assessed by investigator using RECIST 1.1 in each arm
2. Part 2: To evaluate the duration of response (DOR) as assessed by investigator using RECIST 1.1 in each arm
3. Part 2: To evaluate the progression-free survival (PFS) as assessed by investigator using RECIST 1.1 in each arm
4. Part 2: To evaluate the overall survival (OS) in each arm
5. Part 2: To evaluate the safety and tolerability in each arm

Conditions and MedDRA coding

Advanced ccRCC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Has a histologically confirmed diagnosis of unresectable Stage IV (per American Joint Committee on Cancer [AJCC], 8th Edition) RCC with clear-cell component
2. 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
3. Has measurable disease per RECIST 1.1 as assessed by the investigator and verified by blinded independent central review (BICR)
4. Has recovered from all AEs due to previous therapies

Exclusion criteria 11

1. Has hypoxia, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
2. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
3. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
4. Has clinically significant cardiac disease
5. Has moderate to severe hepatic impairment
6. Has a known history of human immunodeficiency virus (HIV) infection
7. Has a history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
8. Has received prior treatment of belzutifan or palbociclib
9. 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
10. Has had major surgery ≤3 weeks prior to first dose of study intervention
11. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1 - Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
2. Part 1 - Number of Participants Who Experience at Least One Adverse Event (AE)
3. Part 1 - Number of Participants Who Discontinue Study Treatment Due to an AE
4. Part 2 - Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

Secondary endpoints 6

1. Part 2 - Clinical Benefit Rate (CBR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
2. Part 2 - Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
3. Part 2 - Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
4. Part 2 - Overall Survival (OS)
5. Part 2 - Number of Participants Who Experience at Least One Adverse Event (AE)
6. Part 2 - Number of Participants Who Discontinue Study Treatment Due to an AE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Yanfang Liu

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Yanfang Liu

Third parties 5

Locations

6 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications