4: LITESPARK-013: Randomized Phase 2 Study of Two Doses of Belzutifan in Patients With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)

Background: In the phase 1 LITESPARK-001 study, the maximum tolerated dose of belzutifan was not reached for doses up to 240 mg/day, and the recommended phase 2 dose (RP2D) regimen was 120 mg once daily. The randomized phase 2 LITESPARK-013 study (NCT04489771) was conducted to examine whether a higher belzutifan dose could improve efficacy while maintaining an acceptable safety profile.

Methods: Patients with advanced ccRCC, measurable disease per RECIST v1.1, ≤3 prior systemic regimens for advanced ccRCC, and disease progression during or after anti–PD-1/L1 therapy were randomly assigned 1:1 to receive oral belzutifan 120 mg once daily or 200 mg once daily. Patients were stratified by IMDC risk (0 vs 1/2 vs 3-6) and number of prior TKI therapies (0 vs 1 vs 2/3). The primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points were DOR and PFS per RECIST v1.1 by BICR, OS, safety, and PK.

Results: Overall, 154 patients were randomly assigned to the 120-mg (n=76) or 200-mg group (n=78). Median follow-up was 20.1 months (range, 14.8-28.4). Efficacy outcomes were similar between groups (Table). Seventy patients (92.1%) in the 120-mg group and 72 (92.3%) in the 200-mg group experienced a treatment-related adverse event (TRAE). Percentages of treatment-related anemia (81.6% with 120 mg; 83.3% with 200 mg) and hypoxia (23.7% with 120 mg; 26.9% with 200 mg) were similar between groups.

Conclusions: The efficacy of belzutifan was similar between patients who received the 120-mg RP2D and those who received a 200-mg dose. The safety of both doses was consistent with the known safety profile of belzutifan. These results support 120 mg orally once daily as the preferred dosage for belzutifan.