Dr Ahmed on the Rationale for Evaluating NTKR-255 After CAR T-Cell Therapy in R/R LBCL

“The rationale behind the study was to give exogenous IL-15 to patients who are receiving CD19-directed CAR T-cell therapy in the hopes of improving outcomes and, potentially, the CAR T-cell fitness itself…without increasing toxicity.”

Sairah Ahmed, MD, an associate professor in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine and director of the CAR T program at The University of Texas MD Anderson Cancer Center, explained the rationale for evaluating NKTR-255 following CD19-directed CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL).

NTKR-255 is an interleukin 15 (IL-15) agonist that has previously demonstrated its ability to improve the efficacy of CAR T-cell therapy, Ahmed began. She noted that patients with LBCL who have higher endogenous levels of IL-15 before receiving CAR T-cell therapy have been shown to have better response rates and outcomes following CD19-directed CAR T-cell therapy. This particular patient population could also benefit from improved T-cell fitness, she added.

In a phase 2 trial (NCT05664217), data of which were presented at the 2025 Transplantation & Cellular Therapy Meetings, patients from the intention-to-treat population treated with NTKR-255 at any dose level following CAR T-cell therapy (n = 11) achieved a 6-month complete response (CR) rate of 73% per blinded independent central review (BICR). The trial also compared NTKR-255 with placebo after CAR T-cell therapy. Patients who received placebo (n = 4) had a CR rate of 50%. Of note, the CR rate and 6-month CR rates were improved without increasing toxicity, specifically regarding cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome.

The rationale of the phase 2 study was to treat patients with LBCL with exogenous IL-15 to patients treated with CD19-directed CAR T-cell therapy with the goal of improving outcomes and CAR T-cell fitness without increasing toxicity, Ahmed concluded.