Cabozantinib (VEGFR/MET/AXL TKI) + nivolumab/ipilimumab extends PFS—but no OS gain—in 1L advanced ccRCC (COSMIC-313)

Cabozantinib, a multi-kinase TKI targeting VEGFR/MET/AXL, was added to nivolumab (PD-1) + ipilimumab (CTLA-4) in the double-blind Phase III COSMIC-313 trial (NCT03937219) in previously untreated advanced clear cell RCC (IMDC intermediate/poor risk; n=855 randomized 1:1). At 45.0 months’ median follow-up, median PFS was 16.6 vs 11.2 months (HR 0.82, 95% CI 0.69–0.98) with triplet vs nivo/ipi, but OS was not improved (HR 1.02, 95% CI 0.85–1.23; p=0.84); grade 3/4 treatment-related AEs were 75% vs 43%. For real-world benchmarking, nivo/ipi historically delivers ~11–12 months median PFS in intermediate/poor-risk disease, while nivo+cabo delivers median PFS ~16–17 months (and ORR ~56%) vs sunitinib—so COSMIC-313’s PFS gain looks directionally similar to “adding a TKI,” but at a substantially higher toxicity cost and without an OS signal in the ITT population.