Belzutifan 120 mg on par with higher dose in advanced clear cell RCC

Use of belzutifan, a first-in-class hypoxia-inducible factor subunit 2α (HIF-2α) inhibitor, in patients with advanced clear cell renal cell carcinoma (RCC) is effective in either the 120- or the 200-mg dose, a phase II study has shown. Both doses are also safe.

A total of 154 patients with advanced clear cell RCC whose disease progressed after one to three prior systemic therapies, including an anti–PD-(L)1 regimen, were enrolled in this study. They were randomly assigned to receive belzutifan 120 (n=76) or 200 mg (n=78) once daily.

The objective response rate (ORR) per RECIST version 1.1 was the primary outcome, while duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety were secondary endpoints.

Over a median follow-up of 20.1 months, the ORR was similar between the 120- and 200-mg dose groups (23.7 percent vs 23.1 percent, respectively; –0.5 percent, 95 percent confidence interval [CI], –14.0 to 12.9; p=0.5312).

The median DOR was 16.1 months for the 200-mg arm and was not reached for the 120-mg arm. There were no differences seen for PFS (hazard ratio [HR], 0.94, 95 percent CI, 0.63–1.40) and OS (medians not reached; HR, 1.11, 95 percent CI, 0.65–1.90) between the two dose groups.

In terms of safety, 35 patients (46.1 percent) in the 120-mg arm and 36 (46.2 percent) in the 200-mg arm experienced grade 3 or 4 treatment-related adverse events.

“These results further support 120 mg once daily as the preferred dose for belzutifan,” the authors said.