A clinical study of belzutifan and zanzalintinib in people with advanced kidney cancer (MK-6482-034)

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

11 May 2026 → ongoing

Decision date (initial)

2026-05-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Exelixis · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-516993-31-00

WHO UTN

U1111-1311-4692

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Safety, Pharmacokinetic, Pharmacogenomic, Pharmacodynamic, Therapy

1. To compare belzutifan + zanzalintinib to belzutifan + placebo with respect to PFS per RECIST 1.1 as assessed by BICR
2. To compare belzutifan + zanzalintinib to belzutifan + placebo with respect to OS

Secondary objectives 5

1. To compare belzutifan + zanzalintinib to belzutifan + placebo with respect to ORR per RECIST 1.1 as assessed by BICR
2. To evaluate the DOR of both treatment arms per RECIST 1.1 as assessed by BICR
3. To evaluate the safety and tolerability of belzutifan + zanzalintinib
4. To evaluate belzutifan + zanzalintinib and belzutifan + placebo with respect to mean change from baseline in HRQoL and disease-related symptoms using the EORTC QLQ-C30 and the FKSI-DRS
5. To evaluate belzutifan + zanzalintinib and belzutifan + placebo with respect to TTD in HRQoL and disease-related symptoms using the EORTC QLQ-C30 and FKSI-DRS

Conditions and MedDRA coding

Renal Cell Carcinoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)
2. Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1
3. Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy

Exclusion criteria 11

1. Has any of the following: a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
2. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
3. Has deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
4. Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
5. Has had major surgery within 8 weeks before randomization
6. Has current pneumonitis/interstitial lung disease
7. Has a history of human immunodeficiency virus infection
8. Has Hepatitis B or Hepatitis C virus infection
9. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
10. Has a history of solid organ transplant
11. Has not adequately recovered from major surgery or has ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression Free Survival (PFS)
2. Overall Survival (OS)

Secondary endpoints 12

1. Objective Response Rate (ORR)
2. Duration of Response (DOR)
3. Number of Participants Who Experience One or More Adverse Events (AEs)
4. Number of Participants Who Discontinue Study Treatment Due to an AE
5. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
6. Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score
7. Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score
8. Change From Baseline in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) (Items 1-9) Score
9. Time to Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
10. TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
11. TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score
12. TTD in Disease Symptoms Using the FKSI-DRS (Items 1-9) Score

Investigational products

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

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ali Rana

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ali Rana

Third parties 5

Locations

9 EU/EEA countries · 53 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 58 files

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

Application history

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