Eftilagimod Alfa (IMP321): A Comprehensive Monograph on a First-in-Class MHC Class II Agonist in Immuno-Oncology

Executive Summary

Eftilagimod alfa, also known as efti or IMP321, is a late-stage, first-in-class investigational immunotherapy developed by Immutep Limited. It is a soluble LAG-3Ig fusion protein engineered to function as a potent Antigen-Presenting Cell (APC) activator. Its mechanism of action represents a novel paradigm in immuno-oncology. Unlike antagonistic anti-LAG-3 monoclonal antibodies that block an inhibitory signal on T-cells, eftilagimod alfa acts as a Major Histocompatibility Complex (MHC) Class II agonist, directly stimulating dendritic cells and monocytes. This primary action initiates a broad, systemic immune response that engages both innate and adaptive immunity, culminating in the robust activation and proliferation of CD8+ cytotoxic T-cells.

Clinically, eftilagimod alfa has demonstrated encouraging anti-tumor activity across multiple solid tumors, particularly when used in combination with anti-PD-1 therapy (pembrolizumab). Key indications where it has shown promise include non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer (MBC). A consistent and highly significant finding across its clinical program is the agent's efficacy in patients with low or negative PD-L1 expression—a population with high unmet medical need and often limited benefit from existing checkpoint inhibitors.

The agent is characterized by a consistently favorable and manageable safety profile. The most common adverse events are low-grade, localized injection site reactions. Crucially, the addition of eftilagimod alfa to checkpoint inhibitors or chemotherapy regimens does not appear to introduce significant additive toxicity, making it an attractive combination partner.