Dr. Iams on the Rationale of Targeting LAG-3 in Advanced NSCLC

Wade T. Iams, MD, assistant professor of medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, discusses the rationale of targeting the LAG-3 pathway in patients with advanced non­–small cell lung cancer (NSCLC).

LAG-3 is an immune checkpoint on the surface of tumor cells, and various monoclonal antibodies, such as relatlimab, are designed to target it, Iams says. LAG-3 is also expressed on antigen-presenting cells, Iams adds.

Unlike monoclonal antibodies, eftilagimod alpha (IMP321) is a soluble LAG-3 molecule designed to act on antigen-presenting cells, Iams explains. This allows for the priming of MHC-II–mediated antigen presentation upstream of T cells, Iams adds.

The combination of eftilagimod alpha and pembrolizumab (Keytruda) is under investigation in patients with advanced or metastatic NSCLC, as part of the phase 2 TACTI-002 trial (NCT03625323). Pembrolizumab is more of a cytotoxic T cell stimulatory agent at the site of cytotoxic T-cell and tumor interactions, according to Iams. Because eftilagimod alpha works upstream at the antigen-presenting cell and T-cell interface, the regimen could serve to increase the overall immune response, Iams concludes.