NKTR-255 enhances complete response following CD19 CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma

Autologous T-cells engineered to express CD19-directed chimeric antigen receptor (CAR) have shown high overall response rates in treatment-refractory large B-cell lymphoma (LBCL).However, more than half of patients do not attain a durable response and will eventually relapse.Thus, strategies to improve long-term efficacy of CAR T-cell products are needed.In this phase 2, randomized, double-blind, placebo-controlled, multicenter study of NKTR-255 versus placebo following CD19 CAR T-cell therapy, eligible patients with R/R LBCL were treated with one of two FDA-approved CAR T-cell products, axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel).In total, 15 patients received CD19 CAR T-cell therapy and received study treatment, 11 patients were randomized to the NKTR-255 group (5 at 1.5 g/kg; 3 at 3.0 g/kg; 3 at 3 g/kg then 6 g/kg cycle 2+) and 4 to placebo.NKTR-255 post CD19 CAR T-cell administration led to augmented CR rates with 8 of 11 (73%) in the NKTR-255 group versus 2 of 4 (50%) in the placebo group reaching complete response rate at month 6 (CR6).Clinical response was accompanied by re-expansion of CD8+ CAR T-cells.The most common (20%) grade 3 NKTR-255-related adverse events were decreased neutrophil, platelet, and lymphocyte counts; all resolved without clinical sequelae.No cytokinerelease-syndrome (CRS) or immune-effector-cell-associated-neurotoxicity-syndrome (ICANS) were reported in the NKTR-255 group.NKTR-255 was well-tolerated, safe, and augmented CR6 for LBCL patients.Based on the findings, additional confirmatory studies with NKTR-255 as adjuvant treatment to CAR T-cell, including other cellular therapies, are warranted (ClinicalTrials.govnumber NCT05664217).