CD371/SAVVY/IL-18 Armored CAR T Clears 3/5 r/r AML in First-in-Human Pilot

CD371/SAVVY/IL-18 is a CLEC12A (CD371/CLL-1)–targeted, IL-18–secreting CAR T built with a mutated CD28 costimulatory domain to limit exhaustion; in the Phase I dose-finding study NCT06017258, 5 patients with relapsed/refractory AML (including 3 post-allo, each refractory to ≥5 prior lines) received a single infusion at 3×10^4 or 3×10^5 cells/kg after lymphodepletion. Robust expansion was observed and 3/5 had AML clearance with no GVHD; dose-limiting toxicities at 3×10^5 were severe CRS and prolonged cytopenias with marrow hypoplasia, prompting de-escalation to 3×10^4. Against benchmarks—DLI after post-transplant relapse induces remissions up to ~29% (with GVHD risk), salvage chemo yields CR ≈29–66% with limited durability, and 1-year OS from post-allo relapse is ≈23%—the early activity at a low dose and absence of GVHD are notable but durability and myelorecovery vs SOC remain unproven.