Exploring the Therapeutic Potential of BI 754111: A LAG-3 Antibody in Concert with Anti-PD-1 for Cancer Treatment

The study explores the role of Lymphocyte Activation Gene-3 (LAG-3), an inhibitory receptor that plays a role in controlling T-cell functions and is implicated in cancer's ability to evade the immune system. BI 754111, a humanized monoclonal antibody, is shown to have a high affinity for LAG-3 and can block its interaction with MHC II. This antibody was tested in various assays for its binding and functional capabilities and was deemed safe in cynomolgus monkeys. Due to its lack of reactivity with mice, a surrogate antibody was used for testing in vivo efficacy in mice. The research found that BI 754111 can moderately enhance the production of IFNγ by exhausted T cells in vitro, especially when combined with another monoclonal antibody, BI 754091, which targets PD-1. This combination resulted in a significant increase in IFNγ secretion.

In vivo studies using mice with MC-38 tumors showed that while BI 754111 alone did not have anti-tumor effects, the combination of BI 754111 with BI 754091 significantly increased the number of complete tumor responses. BI 754111 was found to bind to LAG-3 in cynomolgus monkeys with similar affinity as it does in humans, making it suitable for pharmacokinetic and toxicological assessments. The antibody was well-tolerated in high doses without adverse effects.

The findings suggest a synergistic effect when combining PD-1 and LAG-3 treatments, supporting the ongoing clinical trial for BI 754111 in combination with BI 754091. The research was presented at the American Association for Cancer Research Annual Meeting in 2018.