The addition of the cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitor, ipilimumab to anti-PD-1/L1 monotherapy is currently being evaluated for use in cancers which have failed programmed cell death protein/ligand-1 (PD-1/L1) inhibition alone.4 While combination therapy with CTLA-4 and PD-1/L1 is listed as a treatment option in the NCCN CRC guidelines (V.3.2021),5 ipilimumab has not been comprehensively studied as a second line of therapy in tumors that do not respond to PD-1/L1 inhibition. The gene discussed is CTLA4; the disease is colorectal carcinoma.