NCT05239728

A Study of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Clear Cell Renal Cell Carcinoma Post Nephrectomy (MK-6482-022)

Active, enrolled Phase 3 Last updated 14 August 2025

What this trial tests

Phase 3 trial testing Belzutifan in Carcinoma, Renal Cell in 1,800 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

15 March 2022

Primary endpoint
28 October 2026

28 September 2029

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	1,800
Start date	15 March 2022
Primary completion	28 October 2026
Estimated completion	28 September 2029
Sites	285 locations across Italy, Colombia, Finland, Japan, Malaysia, Taiwan, Ireland, Poland

Drugs / interventions tested

• Belzutifan (BELZUTIFAN) — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →
• Placebo

Conditions studied

• Carcinoma, Renal Cell — all drugs for Carcinoma, Renal Cell →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Renal Cell. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The purpose of this study is to assess the efficacy and safety of oral belzutifan (MK-6482) plus intravenous (IV) pembrolizumab (MK-3475) compared to placebo plus pembrolizumab, in the adjuvant treatment of Clear Cell Renal Cell Carcinoma (ccRCC) post nephrectomy.

The primary study hypothesis is that belzutifan plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.
   Bai R, Li Y, Jian L, Yang Y, et al · · 2022 · cited 200× · PMID 36071472 · DOI 10.1186/s12943-022-01645-2
2. Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.
   Yuan X, Ruan W, Bobrow B, Carmeliet P, et al · · 2024 · cited 144× · PMID 38123660 · DOI 10.1038/s41573-023-00848-6
3. Small molecule inhibitors targeting the cancers.
   Liu GH, Chen T, Zhang X, Ma XL, et al · · 2022 · cited 127× · PMID 36254250 · DOI 10.1002/mco2.181
4. Clear Cell Renal Cell Carcinoma: From Biology to Treatment.
   Kase AM, George DJ, Ramalingam S. · · 2023 · cited 58× · PMID 36765622 · DOI 10.3390/cancers15030665
5. Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the "all-around warrior" in immunotherapy.
   Liu Q, Guan Y, Li S. · · 2024 · cited 50× · PMID 39223527 · DOI 10.1186/s12943-024-02095-8
6. Evolving landscape of first-line combination therapy in advanced renal cancer: a systematic review.
   Lalani AA, Heng DYC, Basappa NS, Wood L, et al · · 2022 · cited 28× · PMID 35782749 · DOI 10.1177/17588359221108685
7. HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects.
   Shi Y, Gilkes DM. · · 2025 · cited 25× · PMID 39825916 · DOI 10.1007/s00018-024-05537-0
8. Emerging Targets in Clear Cell Renal Cell Carcinoma.
   Chen YW, Rini BI, Beckermann KE. · · 2022 · cited 23× · PMID 36230766 · DOI 10.3390/cancers14194843