LITESPARK-003 Phase 2 Results: Belzutifan, Cabozantinib for First- and Subsequent-Line ccRCC

The phase 2 LITESPARK-003 trial examined the efficacy of belzutifan plus cabozantinib for the treatment of advanced clear cell renal cell carcinoma (ccRCC). Initial results demonstrated promising antitumor activity for the combination as a first- and subsequent-line treatment.

Dr. Toni Choueiri, of the Dana-Farber Cancer Institute, presented updated results from cohorts 1 and 2 of the trial at the European Society for Medical Oncology Congress 2023.

Eligible patients involved in the trial had advanced ccRCC and an Eastern Cooperative Oncology Group performance status of 0 or 1. Cohort 1 consisted of 50 patients with no prior systemic therapy for advanced RCC, while cohort 2 included 52 patients who had received prior immunotherapy and 2 systemic regimens for advanced RCC.

All patients received oral belzutifan 120 mg and oral cabozantinib 60 mg once daily. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Most patients (n=28; 56%) in cohort 1 had favorable risk according to the International mRCC Database Consortium, while most patients (n=41; 79%) in cohort 2 had intermediate or poor risk. The median follow-up was 24.3 months (range, 4.1-48.2 months) in cohort 1 and 39.8 months (range, 33.1-55.0 months) in cohort 2. The ORR was 70% in cohort 1 and 31% in cohort 2. Median DOR was 28.6 months (1.9±35.8) in cohort 1 and 31.5 months (4.2±36.8) in cohort 2.

An estimated 57% of all responders in cohort 1 and 51% of responders in cohort 2 remained in response for 24 months or longer. The median PFS was 30.3 months (95% CI, 16-not reached [NR]) in cohort 1 and 13.8 months (95% CI, 9-19) in cohort 2. The median OS was not reached (95% CI, NR-NR) in cohort 1 and 26.7 months (95% CI, 20-41) in cohort 2.

Grade 3-5 treatment-related adverse events (TRAEs) occurred in 23 (46%) patients in cohort 1 and 33 (63%) in cohort 2. No patients died due to a TRAE in cohort 1, and 1 patient (2%) died due to a TRAE (respiratory failure) in cohort 2.

Belzutifan plus cabozantinib demonstrated durable antitumor activity and a consistent safety profile in patients with ccRCC, further supporting the combination of an HIF-2α inhibitor and VEGFR-TKI as a potential treatment option for advanced ccRCC in the first- and subsequent-line settings.