- |||||||||| Anti-MCAM CAR NK / New York Medical College, NKTR-255 / Nektar Therap
Targeting Ewing Sarcoma (ES), Osteosarcoma (OS) and Neuroblastoma (NB) with Anti-Mcam Chimeric Antigen Receptor (CAR) Modified Natural Killer (NK) Cells (Salt Palace Convention Center Ballroom J) - Jan 9, 2022 - Abstract #TCTASTCTCIBMTR2022TCT_ASTCT_CIBMTR_807;
In a preclinical investigation using an orthotopic xenograft mouse model of ES, we found that anti-MCAM CAR NK therapy significantly reduced lung metastasis and prolonged animal survival, and NKTR-255 further enhanced these anti-tumor effects of anti-MCAM CAR NK cells (Fig 1C and D). Our findings demonstrated efficacy of anti-MCAM CAR NK cells alone and/or in combination with NKTR-255 against malignant pediatric solid tumors in vitro and in vivo.
- |||||||||| NKTR-255 / Nektar Therap
Clinical, Journal: NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy. (Pubmed Central) - Jan 6, 2022
P1
Our results show that the novel immunotherapeutic, NKTR-255, retains the full spectrum of IL-15 biology, but with improved PK properties, over rhIL-15. These findings support the ongoing phase 1 first-in-human trial (NCT04136756) of NKTR-255 in participants with relapsed or refractory hematologic malignancies, potentially advancing rhIL-15-based immunotherapies for the treatment of cancer.
- |||||||||| NKTR-255 / Nektar Therap
Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Monotherapy: Study of NKTR 255 in Combination With Cetuximab in Solid Tumors (clinicaltrials.gov) - Dec 30, 2021
P1b/2, N=326, Recruiting,
These findings support the ongoing phase 1 first-in-human trial (NCT04136756) of NKTR-255 in participants with relapsed or refractory hematologic malignancies, potentially advancing rhIL-15-based immunotherapies for the treatment of cancer. N=78 --> 326 | Trial completion date: Apr 2023 --> Aug 2024 | Trial primary completion date: Apr 2022 --> Jun 2023
- |||||||||| Darzalex IV (daratumumab) / J&J, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche, NKTR-255 / Nektar Therap
Clinical, P1 data, Journal, Monotherapy: Phase I study protocol: NKTR-255 as monotherapy or combined with daratumumab or rituximab in hematologic malignancies. (Pubmed Central) - Dec 16, 2021
In preclinical studies, NKTR-255 has demonstrated enhanced proliferation and function of CD8 T cells and natural killer cells, as well as enhanced anti-tumor activity and survival both as monotherapy and in combination with monoclonal antibodies in multiple cancer models. Here, we describe the rationale and design of the first-in-human Phase I, dose-escalation and dose-expansion study of NKTR-255 alone and in combination with daratumumab or rituximab in adults with relapsed/refractory multiple myeloma or non-Hodgkin's lymphoma that will determine the maximum tolerated dose and recommended Phase II dose for NKTR-255.
- |||||||||| NKTR-255 / Nektar Therap
Journal: NKTR-255, a polymer-conjugated IL-15 with unique mechanisms of action on T and natural killer cells. (Pubmed Central) - Dec 1, 2021
NKTR-255 could form soluble complexes with IL-15Rα; binding to murine IL-15Rα generated superagonists that preferentially stimulated NK cells showing that conversion to IL-15Rβ agonist biases the response towards NK cells. These findings highlight the ability of NKTR-255 to utilize IL-15Rα for cis-presentation and act as an IL-15Rαβ agonist on CD8 T cells.
- |||||||||| NKTR-255 / Nektar Therap
Trial completion date: NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma (clinicaltrials.gov) - Aug 18, 2021
P1, N=118, Recruiting,
Taken together, these results support the restoration and expansion of NK cell activity in MM with NKTR-255, providing rationale for its clinical use as a novel immunotherapeutic approach for MM patients alone or in combination with monoclonal antibodies or other immunomodulatory drugs. Trial completion date: Sep 2022 --> Jan 2023
- |||||||||| NKTR-255 / Nektar Therap
[VIRTUAL] NKTR-255, an Engineered IL-15 that Expands NK Cells and CD8+ T Cells for the Treatment of Cancer () - Apr 4, 2021 - Abstract #PEGS2021PEGS_174;
NKTR-255 is an engineered version of native IL-15, designed to have an improved pharmacokinetic profile, preserved binding to all endogenous IL-15 receptors, and to safely increase the proliferation, activity and survival of NK cells and memory CD8+ T cells. We will present preclinical and early clinical data of NKTR-255 in settings of advanced cancer.
- |||||||||| Darzalex IV (daratumumab) / J&J, NKTR-255 / Nektar Therap
[VIRTUAL] Restoring NK Cell Activities in Multiple Myeloma with IL-15 Receptor Agonist NKTR-255 (Channel 11 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4457;
Interestingly, the analysis of immune cells in blood, spleen and tumor tissue from the mice showed that daratumumab depleted, as expected, the total number of NK, CD8+ and CD4+ T cells (mostly at the expense of CD38+ cell subsets); but this depletion was prevented when daratumumab was employed in combination with NKTR-255. Taken together, our studies show that NKTR-255 restores NK cell activities in MM and provide evidences for clinical use of NKTR-255 as novel immunotherapeutic agent in MM alone or in combination with monoclonal antibodies.
- |||||||||| [VIRTUAL] First-in-human phase I study of NKTR-255 in patients with relapsed/refractory hematologic malignancies () - Oct 14, 2020 - Abstract #SITC2020SITC_1386;
P1
Background NKTR-255, an investigational IL-15Rα-dependent polymer-conjugated recombinant human IL-15 (rhIL-15) agonist, maintains the full spectrum of IL-15 biology and provides sustained pharmacodynamic (PD) responses without the need for daily dosing...In preclinical studies, NKTR-255 enhanced antibody-dependent cellular cytotoxicity(ADCC) of each of daratumumab, rituximab, trastuzumab and cetuximab, resulting in synergistic anticancer activity...This 63 y/o male had high-risk recurrent stage III MM with complex cytogenetics (relapsing after VRd, DRd, and carfilzomib plus dexamethasone)...NKTR-255 was well tolerated, with minimal treatment-related toxicities. Our preclinical and preliminary clinical data provide evidence of synergistic effects enhancing ADCC and support continued dose escalation of NKTR-255.
- |||||||||| [VIRTUAL] First-in-human phase I study of NKTR-255 in patients with relapsed/refractory hematologic malignancies () - Oct 14, 2020 - Abstract #SITC2020SITC_651;
P1
Background NKTR-255, an investigational IL-15Rα-dependent polymer-conjugated recombinant human IL-15 (rhIL-15) agonist, maintains the full spectrum of IL-15 biology and provides sustained pharmacodynamic (PD) responses without the need for daily dosing...In preclinical studies, NKTR-255 enhanced antibody-dependent cellular cytotoxicity(ADCC) of each of daratumumab, rituximab, trastuzumab and cetuximab, resulting in synergistic anticancer activity...This 63 y/o male had high-risk recurrent stage III MM with complex cytogenetics (relapsing after VRd, DRd, and carfilzomib plus dexamethasone)...NKTR-255 was well tolerated, with minimal treatment-related toxicities. Our preclinical and preliminary clinical data provide evidence of synergistic effects enhancing ADCC and support continued dose escalation of NKTR-255.
- |||||||||| NKTR-255 / Nektar Therap
Trial completion date, Trial primary completion date: NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma (clinicaltrials.gov) - Aug 16, 2020
P1, N=87, Recruiting,
Role for NKTR255 in providing stemness to CD-19 CAR T cells will also be covered. Trial completion date: Oct 2023 --> Sep 2022 | Trial primary completion date: Apr 2023 --> Apr 2022
- |||||||||| NKTR-255 / Nektar Therap
Trial completion date, Trial primary completion date: NKTR-255 in Relapsed/Refractory Multiple Myeloma & Non-Hodgkin Lymphoma (clinicaltrials.gov) - Jun 15, 2020
P1, N=87, Recruiting,
Trial completion date: Oct 2023 --> Sep 2022 | Trial primary completion date: Apr 2023 --> Apr 2022 Trial completion date: Nov 2021 --> Oct 2023 | Trial primary completion date: May 2021 --> Apr 2023
- |||||||||| Darzalex IV (daratumumab) / J&J, Rituxan (rituximab) / Roche, Biogen, NKTR-255 / Nektar Therapeutics
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 (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6209;
In non-Hodgkin lymphoma (NHL), studies have shown low peripheral blood NK cell counts are associated with poor clinical outcomes in diffuse large B-cell lymphoma patients receiving R-CHOP chemotherapy regimens...The primary objectives of the study are to evaluate: safety, tolerability, MTD, and RP2D of NKTR-255 as a single agent, as well as safety and tolerability of NKTR-255 in combination with daratumumab in patients with r/r MM . Secondary objectives include measures biomarker and pharmacokinetic analyses.
- |||||||||| NKTR-255 / Nektar Therapeutics
Restoring Innate and Adaptive Immune Repertoire in Multiple Myeloma for Therapeutic Application (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6145;
Taken together, our data suggest a significant impact of NKTR-255 on the activation of effector cell function to efficiently target MM cells . This study has important translational implications and highlights the importance of restoring the balance between innate and adaptive immunity in MM.
- |||||||||| NKTR-255 / Nektar Therapeutics
Characterization and comparison of NKTR-255, a polymer-conjugated IL-15 versus IL-15 superagonist (Prince George's Exhibition Halls AB) - Oct 2, 2019 - Abstract #SITC2019SITC_981;
NKTR-255 is a novel IL-15Ralpha dependent molecule that provides enhanced PK and PD properties relative to the native IL-15 cytokine while IL-15 superagonist is a direct engager to IL-2Rbeta complex. These results indicate the potential of NKTR-255 pharmacology to capture the full spectrum of native IL-15 biology.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche, NKTR-255 / Nektar Therapeutics
NKTR-255, a polymer-conjugated IL-15 receptor agonist, enhances efficacy of therapeutic monoclonal antibodies with ADCC activity in solid tumor models (Prince George's Exhibition Halls AB) - Oct 2, 2019 - Abstract #SITC2019SITC_978;
NKTR-255 treatment of NK cells enhanced ADCC activity against tumor cells in vitro and in vivo efficacy of ADCC inducing antibodies in human solid tumor xenograft models. Furthermore, antibody single agent treatment resistant tumor models showed tumor growth inhibition in combination treatment with NKTR-255 suggesting potential for increasing response rates of therapeutic antibodies with ADCC mechanism of action.
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