The following article features coverage from the International Kidney Cancer Symposium 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

MK-6482, a HIF-2α inhibitor, has moved into a phase 3 trial for further testing of its efficacy and safety among patients with previously treated clear cell renal cell carcinoma (ccRCC), according to a poster presented at the 19th Annual Meeting of the International Kidney Cancer Symposium (IKCS 2020).

The Von Hippel Lindau (VHL) tumor suppressor is inactivated among many patients with RCC, resulting in the upregulation of HIF-2α. MK-6482 is a small-molecule inhibitor of HIF-2α that has demonstrated antitumor activity in a phase 1/2 trial among patients with previously treated advanced ccRCC.

The international phase 3 trial is open-label, and will be conducted by centers in the North America, South America, Europe, and parts of Asia. Enrollment has begun, with a planned sample size of 736 patients with advanced ccRCC who have previously received 3 or more prior systemic therapies, including 2 or more doses of an anti–programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) antibody and a vascular endothelial growth factor (VEGF) inhibitor, either separately or in combination.

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Patients will be randomly assigned in a 1:1 ratio to receive oral MK-6482 or everolimus.  Patients will be stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IDMC) prognostic score and number of prior VEGF inhibitor therapies.

The coprimary endpoints will be progression-free survival and overall survival. Secondary endpoints will include objective response rate, duration of response, patient-related outcomes, and safety.

Responses to treatment will be assessed by a blinded independent central review beginning at week 9, then every 8 weeks until week 49, with subsequent evaluation every 12 weeks thereafter, by CT/MRI per RECIST v1.1.

The efficacy analysis will include the intention-to-treat population, defined as all patients who underwent random assignment to a cohort. The safety population will include all patients who received 1 dose or more of the study drug.

Disclosure: Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. For a full list of disclosures, please refer to the abstract.

Read more of Cancer Therapy Advisor‘s coverage of the IKCS 2020 meeting by visiting the conference page.


Choueiri T, Albiges L, Perini R, et al. MK-6482, a hypoxia-inducible factor 2α inhibitor, versus everolimus in heavily pretreated, immune checkpoint inhibitor–resistant, advanced clear cell renal cell carcinoma (ccRCC): phase 3 study. Presented at: 19th Annual Meeting of the International Kidney Cancer Symposium (IKCS 2020); November 6-7, 2020. Abstract TIP139.