In November 2019, the FDA granted breakthrough therapy designation for nivolumab in combination with the anti-CTLA-4 inhibitor ipilimumab for patients with advanced HCC who had previously been treated with sorafenib based on data from the phase I/II CheckMate-040 study of nivolumab plus ipilimumab [38]. This evidence concerns the gene CTLA4 and hepatocellular carcinoma.