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.
NKTR-255 is currently being evaluated in a Phase 1 study in patients with relapsed/refractory (R/R) non-Hodgkin’s lymphoma (NHL) and R/R multiple myeloma (MM) and a Phase 1b/2 trial in combination with ERBITUX® for the treatment of R/R colorectal cancer (CRC) and R/R squamous cell carcinoma of the head and neck (SCCHN).
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.
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