NKTR-255 is an investigational IL‐15 receptor agonist designed to boost the immune system’s natural ability to fight cancer. NKTR-255 increases the proliferation and survival of cancer-killing natural killer (NK) cells and memory CD8+ T cells. NKTR-255 engages the entire IL-15 receptor complex (IL‐15Rα/IL‐15Rβγ) to enhance the formation of long-term immunological memory, which may lead to sustained antitumor immune response.
NKTR-255 is specifically engineered using Nektar’s expertise in polymer chemistry to mimic the natural biological activity of the body’s own IL-15, resulting in optimal activation of the IL-15 pathway. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which has to be given in high doses due to rapid clearance from the body, limiting its utility due to toxicity and lack of convenience and use.
1. Messaoudene M., et al., (2017) Patient’s Natural Killer Cells in the Era of Targeted Therapies: Role for Tumor Killers. Front. Immunol. 8:683.
2. Farnault, L., et al., Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications. Clinical and Developmental Immunology Volume 2012, Article ID 421702, 8 pages
4. Miyazaki T., et al., NKTR-255, a polymer-conjugated IL-15 enhances anti-tumor NK cell responses and synergizes with monoclonal antibodies to provide long-term survival in human lymphoma model. In: Proceedings of the Annual Meeting of the AACR; 2019. Abstract 3265.
63rd American Society of Hematology (ASH) Annual Meeting & Exposition
- Poster 3134: Safety, Tolerability, PK/PD, and Preliminary Efficacy of NKTR-255, a Novel IL-15 Receptor Agonist, in Patients with Relapsed/Refractory Hematologic Malignancies
- Poster 2815: Pharmacodynamic Analysis of CAR-T Cell Persistence in Patients with Hematologic Malignancies Treated with NKTR-255, an IL-15 Receptor Agonist That Enhances CD8+ T-cells: Preliminary Results from a Phase 1 Study
2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- NKTR-255 + Cetuximab in Patients with Solid Tumors: Interim Safety and Efficacy Results from the Phase 1b Dose-escalation Study
2021 European Society for Medical Oncology (ESMO) Congress
- TiP Poster 1026TiP: Phase 1b/2, open-label, multicenter, dose-escalation and dose-expansion study of NKTR-255 plus cetuximab as a salvage regimen in patients with solid tumors
2021 Future Oncology
- Publication: Phase I study protocol: NKTR-255 as monotherapy or combined with daratumumab or rituximab in hematologic malignancies
2021 Journal for ImmunoTherapy of Cancer
62nd American Society of Hematology (ASH) Annual Meeting & Exposition
- Abstract 667: “Restoring NK Cell Activities in Multiple Myeloma with IL-15 Receptor Agonist NKTR-255,” Fernández, F., et al.
- Abstract 825: “Optimizing Ex-Vivo Expanded NK Cell- Mediated Antibody-Dependent Cellular Cytotoxicity (ADCC) Combined with NKTR-255 in Chronic Lymphocytic Leukemia (CLL), Follicular Lymphoma (FL), and Burkitt Lymphoma (BL),” Chu, Y., et al.
2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Abstract 355: “First-in-human phase I study of NKTR-255 in patients with relapsed/refractory hematologic malignancies,” Shah, N., et al.
61st American Society of Hematology (ASH) Annual Meeting & Exposition, Orlando, FL
- Abstract 2866: “Combination of NKTR-255, a polymer conjugated human IL-15, with CD19 CAR T cell immunotherapy in a preclinical lymphoma model,” Chou, C., et al.
- Abstract 4398: “Restoring innate and adaptive immune repertoire in multiple myeloma for therapeutic application,” Fernandez, R., et al.
- TiP Abstract 4459: “A Phase 1, Open-Label, Multi-Center, Dose Escalation and Dose Expansion Study of NKTR-255 As a Single Agent in Relapsed or Refractory Hematologic Malignancies and in Combination with Daratumumab As a Salvage Regimen for Multiple Myeloma,” Shah, N., et al.
2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Abstract P619: “NKTR-255, a polymer-conjugated IL-15 receptor agonist, enhances efficacy of therapeutic monoclonal antibodies with ADCC activity in solid tumor models”, Kivimäe, S., et al.
- Abstract P622: “Characterization and comparison of NKTR-255, a polymer-conjugated IL-15 versus IL-15 superagonist”, Miyazaki, T., et al.
4th Congress of European Hematology Association (EHA)
- Abstract # PS1208: “Effects Of NKTR-255, A Polymer Conjugated Human IL-15, on Efficacy of CD19 CAR T Cell Immunotherapy in a Preclinical Lymphoma Model”, Chou, C., et al.
- Abstract 3265/Poster Board 15: “NKTR-255, a polymer-conjugated IL-15 enhances anti-tumor NK cell responses and synergizes with monoclonal antibodies to provide long-term survival in human lymphoma model”, Miyazaki, T., et al.
2018 ASH 60th Annual Meeting
- “Pharmacokinetic and Pharmacodynamic Study of NKTR-255, a Polymer-Conjugated Human IL-15, in Cynomolgus Monkey”, Miyazaki, T., et al.
- Abstract #418: “Pre-clinical investigation of NKTR-255, a polymer-conjugated IL-15 with a potent NK cell dependent anti-tumor efficacy”, Miyazaki, T., et al.
- Abstract #422: “A polymer-associated human IL-15 (NKTR-255) has optimized biological activity and unique mechanisms of action on CD8 T Cells and NK Cells”, Robinson T., et al.
2018 American Conference on Pharmacometrics (ACoP), San Diego, CA
- Poster T-039: “NKTR-255 Exhibits Target Mediated Drug Disposition and Stimulates Proliferation of Cytotoxic Immune Cells in Cynomolgus Monkeys“
CHI 3rd Annual NK Cell-Based Cancer Immunotherapy Conference, Boston, MA
CHI 2nd Annual Emerging Immuno-Oncology Targets Conference, Boston, MA
- NKTR-255: Accessing IL-15 Therapeutic Potential through Robust and Sustained Engagement of Innate and Adaptive Immunity
Society for Immunotherapy in Cancer (SITC) 32nd Annual Meeting, National Harbor, MD
- Poster #P332: Pre-clinical efficacy and tolerability of NKTR-255, a polymer-conjugated IL-15 for immuno-oncology, Kirk, P., et al.
2017 American Association for Cancer Research (AACR) Annual Meeting
- Abstract 1603/Poster 11: NKTR-255 engages the IL-15 pathway driving CD8 T cell survival and CD8 memory T cell proliferation
2016 SITC Annual Meeting
- Oct 16, 2019: Nektar Therapeutics Announces Initiation of First-in-Human Phase 1 Clinical Study of NKTR-255, an IL-15 Agonist, in Adults with Relapsed or Refractory Non-Hodgkin Lymphoma or Multiple Myeloma
- Apr 2, 2019: Nektar Therapeutics Presents Preclinical Data on its Immuno-Oncology Pipeline Candidates at the American Association for Cancer Research (AACR) Annual Meeting 2019
- Nov 9, 2018: Nektar Therapeutics Presents New Clinical and Preclinical Data for its Immuno-Oncology Pipeline at the 2018 Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Apr 4, 2017: Nektar Therapeutics Presents New Preclinical Data for its Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting