A clinical study of belzutifan and zanzalintinib in people with advanced kidney cancer (MK-6482-033)

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

5 Dec 2025 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · Exelixis

External identifiers

EU CT number

2024-517136-21-00

WHO UTN

U1111-1311-6892

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

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

Secondary objectives 5

1. To compare belzutifan + zanzalintinib to cabozantinib 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 cabozantinib 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 cabozantinib 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, European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV renal cell cancer per AJCC (8th Edition).
2. Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).
3. Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy.
4. Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy.

Exclusion criteria 13

1. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
2. Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization.
3. Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram.
4. Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications.
5. Has not adequately recovered from major surgery or has ongoing surgical complications.
6. Has current pneumonitis/interstitial lung disease.
7. Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization.
8. Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation.
9. Has a serious active nonhealing wound/ulcer/bone fracture.
10. Has a requirement for hemodialysis or peritoneal dialysis.
11. Has history of human immunodeficiency virus infection.
12. Has hepatitis B or hepatitis C virus.
13. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression free survival
2. Overall survival

Secondary endpoints 12

1. Objective Response Rate
2. Duration of Response
3. Number of participants with ≥1 AE(s)
4. Number of participants who discontinue study therapy due to AE(s)
5. Change from baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) global health/health-related quality of life (HRQoL) score
6. Change from baseline in EORTC QLC-C30 physical functioning score
7. Change from baseline in EORTC QLQ-C30 role functioning score
8. Change from baseline in Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) score
9. Time from baseline to first deterioration in EORTC-QLC-C30 global health/HRQoL score
10. Time from baseline to first deterioration in EORTC-QLC-C30 physical functioning score
11. Time from baseline to first deterioration in EORTC-QLC-C30 role functioning score
12. Time from baseline to first deterioration in FKSI-DRS score

Investigational products

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

Test 5

Comparator 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, 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

Rodolfo Perini

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Rodolfo Perini

Third parties 9

Locations

12 EU/EEA countries · 82 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 79 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