The oral hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan was found to have clinical activity in patients with advanced clear cell renal cell carcinoma (ccRCC), according to updated data from a phase 1/2 study. The data were presented at the 2021 Genitourinary Cancers Symposium.

The trial (NCT02974738) included an expansion cohort of 55 patients with previously treated advanced ccRCC. All patients received belzutifan at the recommended phase 2 dose of 120 mg once daily.

Nearly three-quarters of patients (39 of 55) were previously treated with both anti-PD-1 and anti-VEGF agents. Most patients (76%) had intermediate- or poor-risk disease, as determined by International Metastatic RCC Database Consortium (IMDC) criteria.

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At a median follow-up of 27.7 months, 14 patients achieved a partial response (PR). There were no complete responses. Cumulatively, these data translated to an objective response rate of 25%.

Clinical benefit differed by IMDC risk score: Patients who had favorable risk disease achieved a higher PR rate compared vs patients with intermediate- or poor-risk disease (31% vs 24%).

A total of 30 patients had stable disease. When analyzed with the 14 PRs, this led to a disease control rate (DCR) of 80%. Patients with favorable-risk disease had a higher DCR than patients with intermediate- or poor-risk disease (92% and 76%).

The median progression-free survival (PFS) also varied by IMDC risk score. The median PFS was not reached in the subset of patients with favorable-risk disease while patients with intermediate- or poor-risk disease had a median PFS of 11.0 months.

The most common grade 3 adverse events were anemia (27%) and hypoxia (16%). Seven patients died from adverse events, but none of the deaths were treatment-related.

“This study does validate the growing preclinical and clinical evidence that HIF-2a inhibition may offer an effective and well-tolerated treatment for patients with advanced renal cell carcinoma,” said Todd Bauer, MD, who presented the findings.

A phase 3 trial is currently evaluating belzutifan in patients with previously treated ccRCC (NCT04195750).

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This research was supported by Merck Sharp & Dohme Corp.


Bauer TM, Choueiri TK, Papadopoulos KP, et al. The oral HIF-2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma (RCC): updated follow-up of a phase I/II study. Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 273.

This article originally appeared on Cancer Therapy Advisor