NKTR-255 (IL-15R agonist) Lifts 6-mo CR After CD19 CAR-T in R/R LBCL

Phase 2, randomized, double-blind, placebo-controlled multicenter study (NCT05664217) tested NKTR-255—an IL-15 receptor agonist designed to expand CD8 T and NK cells—given after axi-cel or liso-cel in relapsed/refractory large B-cell lymphoma (n=15 treated; 11 NKTR-255 across dose levels, 4 placebo). Month-6 complete response (CR6) was 73% (8/11) with NKTR-255 vs 50% (2/4) with placebo; responses coincided with re-expansion of CD8+ CAR T cells. Common grade≥3 NKTR-255–related AEs were cytopenias (neutrophils, platelets, lymphocytes ≥20%), all resolving; no CRS/ICANS occurred with NKTR-255. As context, standard CD19 CAR-T alone yields CR ≈58% with axi-cel and 53% with liso-cel and ~41% 2-yr PFS (TRANSCEND), so the small randomized signal suggests a potential deepening of remission, albeit on limited numbers and a different endpoint.