KEY TAKEAWAYS
- The MK-6482-003 phase II trial aimed to evaluate the updated efficacy and safety results of belzutifan+cabozantinib in cohorts 1 and 2 of the advanced ccRCC study.
- The primary endpoint was ORR. Secondary endpoints included DOR, PFS, OS, and safety.
- The result demonstrated the potential of belzutifan+cabozantinib as a promising therapy for advanced ccRCC.
Early results from the LITESPARK-003 study indicate that belzutifan plus cabozantinib exhibits promising antitumor activity in both first-line and subsequent-line treatment settings for advanced clear cell renal cell carcinoma(ccRCC) patients(pts).
For this study, researchers aimed to evaluate the updated efficacy and safety results of belzutifan+cabozantinib in cohorts 1 and 2 of the advanced ccRCC study.
The study included advanced ccRCC pts with an ECOG performance status of 0 or 1. Cohort 1 comprised pts with no prior systemic therapy for advanced RCC, while Cohort 2 consisted of pts who had received prior immunotherapy and up to two systemic regimens for advanced RCC. All pts were administered oral belzutifan 120 mg and oral cabozantinib 60 mg once daily.
The primary endpoint was the objective response rate (ORR) per RECIST v1.1 assessed by investigators. Secondary endpoints encompassed duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
In cohort 1, comprising 50 pts, (n = 28; 56%) had IMDC favorable risk, while in cohort 2 (52 pts), (n = 41; 79%) had IMDC intermediate/poor risk. Median follow-up was 24.3 months (range, 4.1-48.2) in cohort 1 and 39.8 months (range, 33.1-55.0) in cohort 2. The median DOR was 28.6 months (range, 1.9+ to 35.8) in cohort 1 and 31.5 months (range, 4.2+ to 36.8) in cohort 2, with 57% and 51% of responders remaining in response for ≥24 months in each cohort, respectively.
The median PFS was 30.3 months (95% CI, 16-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. Overall, 46% of pts in Cohort 1 and 63% in Cohort 2 experienced grade 3-5 treatment-related adverse events (TRAE). No pts died due to a TRAE in cohort 1, while 1 patient (2%) in cohort 2 died due to a TRAE (respiratory failure).
The result demonstrated the potential of belzutifan+cabozantinib as a promising therapy for advanced ccRCC.
Clinical Trial: https://clinicaltrials.gov/study/NCT03634540
T.K. Choueiri1, T. Bauer2, J.R. Merchan3, D.F. McDermott4, R. Figlin5, E. Arrowsmith6, M.D. Michaelson7, E. Heath8, A.A. D’Souza9, S. Zhao10, L. Mhamdi11, R. Perini11, D. Vickery12, S. Tykod. Annals of Oncology (2023) 34 (suppl_2): S1254-S1335. 10.1016/annonc/annonc1358.
