LITESPARK-12 tested Len/pem/bel (VEGF/PD1/HIF) vs Len/pem in 1st line RCC #ESMO26 (supported by a RII +ve PFS R2 @AlbigesL @crisuarez08). In the R3 both PFS and OS hasd HRs~1 with ⬆️ tox for triplets. Belzutifan doublets seem active so why do the triplets fail. It’s likely due to the increased toxic compromising dose intensity of the extremely active Len/pem (2 yr PFS). There seems a limit to tolerable drug intensity- triplets (COSMIC313 too) maybe a step too far. @OncoAlert @DrChoueiri