Randomized phase 2 dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma

Highlights•No differences were observed in ORR for belzutifan 200 mg QD and 120 mg QD (23.1% vs 23.7%; one-sided P = 0.5312)•Similar clinical outcomes for belzutifan 200 mg and 120 mg dose groups were also observed for DOR, PFS, and OS•More dose modifications and treatment discontinuations due to AEs were observed with belzutifan 200 mg than 120 mg•These results further support 120 mg QD as the preferred dose for belzutifanAbstractBackgroundBelzutifan is a first-in-class HIF-2α inhibitor approved at a dose of 120 mg once daily for certain adults with VHL disease and adults with advanced renal cell carcinoma (RCC) following therapy with a programmed death receptor (or ligand)-1 (PD-[L]1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor. However, whether belzutifan dose could be optimized is unclear.Patients and methodsThe phase 2 LITESPARK-013 study (NCT04489771) enrolled patients with advanced clear cell RCC whose disease progressed after 1-3 prior systemic therapies, including an anti–PD-(L)1 regimen. Patients were randomly assigned 1:1 to receive belzutifan 120 mg or 200 mg once daily. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.ResultsOverall, 154 patients were enrolled (120 mg: n = 76; 200 mg: n = 78). Median follow-up was 20.1 months (range 14.8-28.4). ORR was 23.7% vs 23.1% for the 120 mg and 200 mg groups, respectively (P = 0.5312; −0.5% [95% CI, −14.0 to 12.9]. Median DOR was not reached for the 120 mg arm and was 16.1 months (2.1+ to 23.5+) for the 200 mg arm. No between-group differences were observed for PFS (HR 0.94 [95% CI 0.63-1.40]) or OS (medians not reached; HR 1.11 [95% CI, 0.65-1.90]). Grade 3 or 4 treatment-related adverse events were observed in 35 patients (46.1%) in the 120 mg group and 36 patients (46.2%) in the 200 mg group.ConclusionThe efficacy of belzutifan was similar between the 120-mg dose and the 200-mg dose for previously treated clear cell RCC. Safety at both doses was consistent with the known safety profile of belzutifan. These results further support 120 mg once daily as the preferred dose for belzutifan.