Nektar announces presentations on NKTR-255 at ASH annual meeting

Nektar Therapeutics announced two presentations of NKTR-255 at the 64th American Society of Hematology Annual Meeting. NKTR-255 is an investigational IL-15 receptor agonist designed to boost antitumor immunity by increasing the proliferation and survival of natural killer and memory CD8+ T cells, thereby enhancing the formation of long-term immunological memory, which may lead to sustained antitumor immune response. The study design of an upcoming Phase 2/3, randomized, double-blind, placebo-controlled, multicenter clinical trial of NKTR-255 following CD19-directed chimeric antigen receptor T cell therapy in patients with relapsed/refractory large B-cell lymphoma was presented by Miguel-Angel Perales, M.D., Chief, Adult Bone Marrow Transplant Service, at Memorial Sloan Kettering Cancer Center on Sunday, December 11th. Pre-clinical studies demonstrate that NKTR-255 can potentiate the effects of CAR-T therapies and a number of early clinical studies are currently underway to evaluate the role of NKTR-255 following CAR-T cell treatment for different hematologic malignancies. Additionally, results from the ongoing Phase 1 study of NKTR-255 as a monotherapy and in combination with daratumumab in patients with R/R multiple myeloma or non-Hodgkin’s lymphoma were presented by Krina Patel, M.D., Associate Professor, Department of Lymphoma-Myeloma, at the University of Texas MD Anderson Cancer Center on Monday, December 12th. The data showed that NKTR-255 resulted in an expansion and proliferation of NK cells following daratumumab’s on-target depletion of CD38-expressing NK cells. Abstract 3335: "A Phase 2/3, Randomized, Double Blind, Placebo-Controlled, Multicenter Study of NKTR-255 Vs Placebo Following CD-19 Directed CAR-T Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma", Perales M., et al. Based on preclinical and clinical evidence, NKTR-255 has the potential to improve efficacy of currently approved cellular therapy by enhancing antitumor effect and durability of responses. The upcoming Phase 2/3 study will enroll eligible patients with R/R LBCL who have received an FDA-approved CAR-T cell product. Patients will receive NKTR-255 intravenously, starting approximately 14 days following CAR-T therapy, with continued dosing every 21 days. The primary objective of the Phase 2 portion of the study is to identify the dose of NKTR-255 for the Phase 3 portion of the study based on safety, tolerability, and complete response rate at month 6, the primary efficacy endpoint. Abstract 4652: "Safety, Tolerability, PK/PD and Preliminary Efficacy of NKTR-255, a Novel IL-15 Receptor Agonist, in Patients with Relapsed/Refractory Hematologic Malignancies", Patel K., et al. NKTR-255 was well tolerated in heavily pre-treated patients with hematologic malignancies in doses up to 12 undefined/kg and in combination with daratumumab in doses up to 9 undefined/kg. The majority of treatment-related adverse events were low-grade, transient, and easily managed. The maximum tolerated dose was not reached.No new safety signals or overlapping toxicities were observed with the doublet and dose escalation is ongoing. Early evidence of clinical activity was observed in this heavily pre-treated and highly refractory patient population with the doublet. Peak fold-changes of ~17-fold NK cell and ~2-fold in CD8+ T cell expansion were observed in the first 2 cycles with NKTR-255 monotherapy doses up to 12 undefined/kg. Sustained proliferative ability of NK and CD8+ T cells across multiple cycles indicated no evidence of tachyphylaxis. Preliminary data from patients previously treated with off-the-shelf allogenic CAR-T cells indicate that allo-CAR-T cells persisted with NKTR-255 monotherapy, suggesting no alloreactivity to off-the-shelf allo-CAR-T cells.With combination therapy, NK cell rescue was observed with sustained increases in NK and CD8+ T cells despite daratumumab’s on-target depletion of CD38 expressing NK cells.