Kelley RK, Sangro B, Harris W, et al. - In this phase I/II study, researchers assessed tremelimumab (anticytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) for the treatment of unresectable hepatocellular carcinoma (HCC), when administered to patients as monotherapies as well as in combination. They also assessed a novel regimen featuring a single, priming dose of tremelimumab. Participants included HCC patients who experienced progression on, were intolerant to, or refused sorafenib. These were randomized to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks). Findings demonstrated tolerability as well as clinical activity of all regimens; the most encouraging benefit-risk profile was shown by the T300 + D regimen. An association of an early expansion of CD8+ lymphocytes with the response across arms was identified; the T300 + D arm had the highest proliferating CD8+ lymphocyte levels. T300 + D regimen’s unique pharmacodynamic activity as well as link with objective response rate lend further support to its continued assessment in HCC.