The following article features coverage from the 2021 Genitourinary Cancers Symposium meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan showed promising antitumor activity in combination with cabozantinib in patients with previously treated metastatic clear cell renal cell carcinoma (ccRCC), according to study data presented at the 2021 Genitourinary Cancers Symposium.1

Toni K. Choueiri, MD, of Dana Farber Cancer Institute, presented results from cohort 2 of the phase 2 study (NCT03634540). Cohort 1 tested the combination in patients who were treatment-naïve.

The study enrolled patients with metastatic disease who had received no more than 2 prior lines of treatment. Initially, 6 patients in either cohort 1 or 2 were treated with 120 mg of belzutifan and 60 mg of cabozantinib once daily for 21 days.

Continue Reading

A safety evaluation conducted in the first 6 patients identified one case of hand-foot syndrome, which comprised the only dose-limiting toxicity observed. Based on this finding, the investigators moved forward with a recommended phase 2 dose of 120 mg belzutifan/60 mg cabozantinib.

In this preliminary analysis, the results from which were presented at the medical meeting, efficacy was evaluated in patients who received at least 1 dose of study treatment and had 6 or more months of follow-up. Data showed that the confirmed overall response rate was 22.0%, which included 9 partial responses. Most patients (90.2%) had tumor shrinkage.

The disease control rate was 92.7%, and the median duration of response had not been reached at the time of the analysis. All responses are ongoing, Choueiri said.

Regarding survival, the median progression-free survival was 16.8 months (95% CI, 9.2-not reached); the 6-month PFS rate was 78.3%. At 6 months, the overall survival rate was 95.0%.

53 patients were included in the safety analysis. Treatment-related adverse events (TRAEs) affected 98.1% of patients, though most were grade 1 or grade 2.

The most common grade 3 TRAEs were hypertension (22.4%), anemia (11.3%), fatigue (11.3%), and an increase in alanine transaminase (ALT; 5.7%). Additionally, 2 patients had grade 3 hypoxia.

There were no grade 4 TRAEs or deaths. Treatment discontinuation due to TRAEs was observed in 11.3% and 15.1% of patients due to belzutifan and cabozantinib, respectively.

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 clinical trial was supported by Merck Sharp & Dohme Corp.

Read more of our coverage of the 2021 Genitourinary Cancers Symposium by visiting the conference page.


Choueiri TK, Bauer TM, McDermott DF, et al. Phase 2 study of the oral hypoxia-inducible factor 2α (HIF-2α) inhibitor MK-6482 in combination with cabozantinib in patients with advanced clear cell renal cell carcinoma (ccRCC). Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 272.