Eftilagimod alfa (soluble LAG-3/MHC class II APC activator) links early ALC rise to ~7.7-mo OS gain across metastatic cancers

Eftilagimod alfa (E; soluble LAG-3 fusion protein that agonizes a subset of MHC class II on antigen-presenting cells to drive Th1/T-cell activation) was analyzed across 5 studies in late-stage metastatic NSCLC/HNSCC/melanoma/breast cancer (n=569), given as 30 mg SC biweekly (then q2–4w maintenance) with pembrolizumab (P) or weekly paclitaxel (C) versus control arms. E significantly increased absolute lymphocyte count (ALC) by ~3 months and sustained it to ~12 months (p=0.03), with 54.4% ALC “responders” on E (vs 40.4% in control); ALC responders on E had median OS 23.4 vs 15.7 months (HR 0.69; p=0.002), while ALC responders in control did not (20.4 vs 17.4 months; HR 0.98; p=0.93). Correlative biology supported mechanism—clinical responders (iPR/iCR) showed on-treatment upregulation of T-cell/NK/cytotoxicity pathways (GEP subset n=111), and IFN-γ/CXCL10 rose ~8h after first E dose and remained elevated to next dose (subset n=79); however, efficacy here is biomarker-correlative (ALC) rather than a randomized, regimen-level OS win versus today’s NSCLC immuno-chemo SOC (e.g., pembrolizumab + chemo mOS ~15.9 vs 11.3 months in KEYNOTE-407) or PD-L1–high pembrolizumab monotherapy (mOS ~26.3 vs 13.4 months in KEYNOTE-024).