NKTR-255 Enhances CAR-T Therapy Response in Relapsed/Refractory Large B-Cell Lymphoma
核心洞察
Nektar Therapeutics' NKTR-255, an IL-15 (搜索) agonist, significantly improved complete response rates (CRR) in lymphoma (搜索) patients after CAR-T therapy.
In a Phase 2 study, 73% of patients treated with NKTR-255 achieved complete response at six months, compared to 50% in the placebo group.
NKTR-255 enhances CAR-T cell kinetics, leading to a 5.8-fold increase in CD8+ CAR-T area under the curve (AUC) compared to placebo.
Nektar Therapeutics announced positive results from its Phase 2 proof-of-concept study of NKTR-255, an investigational IL-15 (搜索) agonist, in patients with relapsed/refractory large B-cell lymphoma (搜索) (LBCL) following CD19-directed CAR-T therapy. The study, presented at the 66th Annual ASH Meeting, demonstrated a significant boost in complete response rates (CRR) with the addition of NKTR-255.
The multicenter, double-blind trial randomized patients to receive NKTR-255 or placebo intravenously, starting 14 days post-CAR-T infusion. The NKTR-255 group showed a 73% CRR at six months, compared to 50% in the placebo group, as assessed by blinded independent central radiology review. Notably, two patients in the NKTR-255 arm converted from stable disease or partial response to complete response at six months, a change not observed in the placebo arm.
Enhanced CAR-T Cell Kinetics
NKTR-255 is designed to enhance natural killer (NK) and CD8+ T-cell activity, aiming to improve the durability and effectiveness of CAR-T therapies by promoting the survival and expansion of memory CD8+ T-cells. The trial results indicated that NKTR-255 treatment led to enhanced CAR-T cell kinetics, with a 5.8-fold increase in the CD8+ CAR-T area under the curve (AUC) 0-15 days post-administration compared to placebo.
Clinical Significance
Dr. Sairah Ahmed, Associate Professor at the University of Texas MD Anderson Cancer Center, emphasized the clinical significance of these findings. "The results of this study demonstrated that NKTR-255 enhanced CAR T-cell counts and increased the number of patients who achieve a CR at 6 months post infusion. This finding is highly significant since, in multiple pivotal trials, patients who achieved complete response at 6 months were highly likely to remain in complete response beyond 2 years translating to improved progression-free survival."
The observed clinical benefit surpasses historical benchmarks for current commercial CD19 CAR T-cell therapies, which report 6-month complete response rates ranging from 41% to 44%.
Safety and Tolerability
NKTR-255 was found to be safe and well-tolerated in patients with relapsed/refractory LBCL when combined with FDA-approved CD19 CAR T-cell products.
Future Directions
Dr. Mary Tagliaferri, Chief Medical Officer of Nektar, highlighted that this study is the first randomized trial demonstrating that adjuvant treatment with NKTR-255 can enhance the durability of response to standard-of-care commercial CAR T-cell therapy by modifying CAR T-cell kinetics. NKTR-255 is also being investigated in other clinical trials, including studies for anti-PD1 resistant metastatic non-small cell lung cancer and as a maintenance treatment in metastatic urothelial carcinoma (搜索).