INDICATION: Hematological Malignancies
Discovered and wholly owned by Nektar
NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway and expand natural killer (NK) cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of long-term immunological memory, which may lead to sustained anti-tumor immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which is rapidly cleared from the body and must be administered frequently and in high doses, limiting its utility due to toxicity and convenience of use.
One of the big challenges in treating cancer patients with targeted monoclonal antibodies is that the cancer patients have a deficiency in key effector cells like NK cells that are needed to work with the monoclonal antibodies.1,2 In nonclinical studies, NKTR‑255 exhibited anti-tumor activity and substantially enhanced in vivo proliferation and activation of NK cells to provide sustained cytotoxic function.3 In a preclinical lymphoma model where single agent daratumumab was ineffective, NKTR-255 treatment, in combination with daratumumab, increased NK cell numbers and activity in bone marrow tissue and enhanced ADCC-mediated tumor cell clearance in the bone marrow compartment.4
In oncology, NKTR-255 is being evaluated in combination with T cell redirection therapies, novel CAR-Ts, anti-HER2 antibodies and anti-CD20 antibodies via an ADCC-focused mechanism in preclinical models of liquid and solid tumors. NKTR-255 is also being evaluated in combination with anti-retroviral and immune modulator therapies through a research collaboration with Gilead.
About the Phase 1 Study
The NKTR-255 Phase 1 study is an open-label, dose escalation and dose expansion study in patients with select hematological malignancies (relapsed or refractory NHL or MM). The dose escalation phase of the study will evaluate the safety and tolerability of NKTR-255 as monotherapy in approximately 40 patients in order to establish a recommended Phase 2 dose (RP2D) for NKTR-255. The dose expansion phase of the study will enroll in two separate cohorts: the first cohort will enroll patients with MM or NHL (relapsed salvage) to evaluate the NKTR-255 RP2D as a monotherapy and the second cohort will enroll patients with MM or NHL (relapsed/refractory salvage) to evaluate the NKTR-255 RP2D in combination with targeted antibodies, including anti-CD38 monoclonal antibody, daratumumab. The study will also evaluate pharmacokinetic and pharmacodynamic effects, anti-tumor activity and biomarker assessments.
For more information, please visit clinicaltrials.gov
1Messaoudene M., et al., (2017) Patient’s Natural Killer Cells in the Era of Targeted Therapies: Role for Tumor Killers. Front. Immunol. 8:683.
2Farnault, 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
3 Journal for ImmunoTherapy of Cancer 2017 5(Suppl 2):87; P332.
4Miyazaki 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.
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