zanzalintinib + nivolumab + relatlimab

A three-drug investigational combination consisting of zanzalintinib, a small molecule multi-targeted tyrosine kinase inhibitor (TKI), nivolumab, an immune checkpoint inhibitor targeting PD-1, and relatlimab, an immune checkpoint inhibitor targeting LAG-3. Zanzalintinib blocks signals that promote tumor growth by targeting multiple receptor tyrosine kinases, including VEGFR, MET, and the TAM family. Nivolumab blocks PD-1 to boost T-cell mediated immune responses against cancer, and relatlimab blocks LAG-3, an inhibitory immune checkpoint, further enhancing T-cell activity. This triplet is under investigation for the treatment of advanced/untreated clear cell renal cell carcinoma and other advanced solid tumors. Clinical data show the triplet is generally tolerable but may increase adverse event rates compared to doublet therapy (zanzalintinib + nivolumab).