BC3402 w/ Tremelimumab + Durvalumab (STRIDE) in Hepatocellular Carcinoma

Brief Background/Rationale Hepatocellular carcinoma (HCC) is the most common liver cancer and the fastest rising cause of cancer-related deaths in the U.S. Immune checkpoint inhibitors (ICIs) proved to be highly efficacious in HCC and the dual ICIs combination, tremelimumab plus durvalumab, is a standard front-line treatment for advanced and metastatic HCC. However, the response rate of the dual ICIs regimen is about 20% and participants invariably progress. There is a need for more efficacious treatment. T cell immunoglobulin mucin-3 (TIM3) is highly expressed on multiple immune cells and plays a complex role in regulating immune responses and inducing immune tolerance. BC3402 is a TIM3 targeting inhibitory humanized IgG4 subtype monoclonal antibody which displays synergistic anti-tumor effects when combined with agents targeting PD1 and CTLA4 in preclinical tumor models as well as in the first in human (FIH) trial. Investigators hypothesize that the co-targeting of TIM3 will significantly increase the anti-tumor efficacy of dual targeting of PD1/PDL1 and CTLA4 axes in HCC and thus propose a clinical trial to investigate the efficacy of a novel triplet ICI combination of BC3402 plus the STRIDE regimen in participants with advanced, unresectable treatment-naïve HCC.