LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy.

The first-in-class, small molecule HIF-2α inhibitor, belzutifan, has demonstrated promising antitumor activity in previously treated patients with clear cell renal cell carcinoma (RCC). HIF-2α also regulates VEGF expression and is involved in resistance to anti-VEGF therapy. This study describes the rationale and design for a randomized, phase III study evaluating efficacy and safety of belzutifan plus the tyrosine kinase inhibitor (TKI) lenvatinib versus the TKI cabozantinib in patients with advanced RCC progressing after anti-PD-1/PD-L1 therapy in the first- or second-line setting or as adjuvant therapy. Considering the unmet need for effective and tolerable treatment of advanced RCC following immune checkpoint inhibitors, belzutifan plus lenvatinib may have a positive benefit/risk profile. Clinical Trial Registration: NCT04586231 (

Future oncology (London, England). 2023 Feb 08 [Epub ahead of print]

Robert J Motzer, Manuela Schmidinger, Masatoshi Eto, Cristina Suarez, Robert Figlin, Yanfang Liu, Rodolfo Perini, Yayan Zhang, Daniel Yc Heng

Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Medical University of Vienna, Vienna, 1090, Austria., Kyushu University Hospital, Fukuoka, 812-8582, Japan., Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, 08035, Spain., Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Merck & Co., Inc., Rahway, NJ 07065, USA., Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada.