Dr Albiges on the Efficacy of Lenvatinib Plus Belzutifan in ccRCC

“We are eagerly waiting [for the LITESPARK-011] trial to read out, given the great signal of activity that we have [seen with belzutifan plus lenvatinib] in the KEYMAKER-U03 study.”

Laurence Albiges, MD, PhD, head of the Department of Oncology at Institut Gustave Roussy, discussed key findings from a cohort of substudy 03B of the phase 1 KEYMAKER-U03 trial (NCT04626518) investigating belzutifan (Welireg) plus lenvatinib (Lenvima) in patients with advanced clear cell renal cell carcinoma (ccRCC).

The randomized, phase 1 KEYMAKER-U03 trial is designed to evaluate various combination regimens in patients with advanced ccRCC who have progressed on at least 1 prior VEGF-TKI and 1 PD-1 inhibitor. Multiple combinations have been explored in this study, including pembrolizumab (Keytruda) plus quavonlimab (formerly MK 1308), pembrolizumab plus favezelimab (MK-4280), pembrolizumab plus MK-4830, pembrolizumab plus belzutifan, pembrolizumab plus lenvatinib, and lenvatinib plus belzutifan (arm B5).

Key findings from this trial include those from arm B5 (n = 64), which demonstrated the efficacy of lenvatinib plus belzutifan, Albiges said. Lenvatinib is a potent VEGF TKI, and belzutifan is a first-in-class HIF-2α inhibitor. Notably, at a median follow-up of 17.6 months (range, 6.5-35.9), this combination elicited a relatively high overall response rate in KEYMAKER-U3, at 46.9 months, including 1 complete response and 29 partial responses, Albiges explained. The median duration of response in this arm was 22.1 months (95% CI, 1.4+ to 32.8+).

The promising activity observed with belzutifan plus lenvatinib in KEYMAKER-U03 has generated interest for findings from the ongoing phase 3 LITESPARK-011 trial (NCT05239728), which has completed enrollment, according to Albiges. This study is investigating lenvatinib plus belzutifan vs standard-of-care cabozantinib (Cabometyx) in patients with ccRCC who have previously progressed on both a VEGF-TKI and a PD-1 inhibitor. The encouraging preliminary findings from KEYMAKER-U03 have raised strong anticipation for the LITESPARK-011 readout, which will further clarify the clinical relevance of lenvatinib plus belzutifan, Albiges concluded.