Belzutifan 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.
The 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.
Overall, 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.
The 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.
Annals of oncology : official journal of the European Society for Medical Oncology. 2024 Sep 02 [Epub ahead of print]
N Agarwal, J Brugarolas, P Ghatalia, S George, J B Haanen, H Gurney, R Ravilla, A Van der Veldt, B Beuselinck, I Pokataev, B B M Suelmann, M H Tuthill, D Vaena, F Zagouri, J Wu, R F Perini, Y Liu, J Merchan, M B Atkins
Clinical Translation, Cancer Research, Genitourinary Oncology Program, Huntsman Cancer Institute, University of Utah (NCI-CCC), Salt Lake City, UT, USA. Electronic address: ., Kidney Cancer Program, Simmons Comprehensive Cancer Center, and Internal Medicine - Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA., Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands., MQ Health, Macquarie University, Sydney, Australia., New York Oncology Hematology, Albany, NY, USA., Medical Oncology and Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, Netherlands., Oncology, UZ Leuven, Leuven, Belgium., Oncology, City Clinical Oncology Hospital No. 1, Moscow, Russia., Oncology, Universitair Medisch Centrum Utrecht, Utrecht, Netherlands., Oncology and Haematology, Oxford University Hospitals NHS Foundation Trust, United Kingdom., Oncology, West Cancer Center and Research Institute, Germantown, TN, USA., Oncology, Alexandra Regional General Hospital Athens, Greece., Oncology, Merck & Co., Inc., Rahway, NJ, USA., Oncology, University of Miami - Sylvester Comprehensive Center Cancer, Miami, FL, USA., Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA.