Dr Ahmed on the Safety Profile of NKTR-255 in Relapsed/Refractory LBCL

"[According to] these preliminary data, it does not seem that NKTR-255 increases the risk of CRS or ICANS. [During] the maintenance time period when they got NKTR-255, the main toxicities were hematologic and a few fevers, [which] all resolved without tocilizumab or steroids."

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, discussed key safety data from a phase 2 trial (NCT05664217) evaluating the interleukin-15 agonist NKTR-255 in patients with relapsed/refractory large B-cell lymphoma (LBCL).

Data from the trial were presented during the 2025 Transplantation & Cellular Therapy Meetings and demonstrated the clinical activity of NKTR-255 in patients with relapsed/refractory hematologic malignancies following CAR T-cell therapy. In the intention-to-treat population, the 6-month complete response rate per blinded independent central review was 73% among patients who received NKTR-255 (n = 11) compared with 50% among patients who received placebo (n = 4).

NKTR-255 was administered on day 7 post–CAR T-cell infusion, Ahmed stated. This timing was selected to minimize the risk of overlapping toxicities, such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), she explained. Notably, no increases in CRS or ICANS were observed following NKTR-255 administration, Ahmed reported.

The trial required patients to meet initial trial inclusion criteria and subsequently undergo a second assessment to confirm adequate clinical status prior to receiving NKTR-255, Ahmed continued. Those who met the second set of criteria tolerated NKTR-255 without unexpected toxicities, she noted. During the maintenance phase, the most commonly reported adverse effects were hematologic toxicities and low-grade fevers, which resolved without the need for corticosteroids or tocilizumab (tocilizumab; Actemra), Ahmed added.Overall, these early data suggest that NKTR-255 may be a well-tolerated and efficacious approach to improving outcomes following CAR T-cell therapy, Ahmed concluded.

Disclosures: Ahmed has received institutional support for clinical trials from Caribou, Chimagen, Genmab, Janssen, KITE/Gilead, Merck, Nektar, and Xencor; is a member of the Chimagen scientific advisory committee; serves on the Data Safety Monitoring Board for Myeloid Therapeutics; and serves as a consultant for ADC Therapeutics, Bristol Myers Squibb, and KITE/Gilead Sciences.