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**RXC004 + nivolumab** is a combination regimen under clinical investigation for genetically selected metastatic colorectal cancer. RXC004 (Zamaporvint) is a potent, selective, orally active small molecule inhibitor of *Porcupine*, a key enzyme in the Wnt signaling pathway. Porcupine inhibition blocks release of Wnt ligands, preventing both tumor growth and immune evasion. Nivolumab is a monoclonal antibody that inhibits *Programmed cell death protein 1 (PD-1)*, restoring anti-tumor immune response. The combination aims to target both Wnt-dependent oncogenic signaling and tumor immune suppression, potentially overcoming resistance to immunotherapy in microsatellite stable colorectal cancers with RNF43 mutation or RSPO gene fusion[4][5][1][3].
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