NKTR-262
NKTR-262 in combination with bempegaldesleukin
INDICATION: Locally Advanced or Metastatic Solid Tumor Malignancies
Discovered and wholly owned by Nektar
Unpartnered
About NKTR-262
Cancer treatments that couple pharmacological activation of tumor antigen presentation with activation and expansion of CD8+ T and natural killer (NK) cells in the tumor environment have the potential to induce an effective anti-tumor immune response in patients. NKTR-262 is a novel small molecule agonist designed to activate toll-like receptors (TLRs). Intratumoral delivery of NKTR-262 promotes TLR activation to induce the development of antigen-specific immunity by initiating the process by which the immune system generates antigen-specific cytotoxic T cells to the patient’s specific tumor.1 Bempegaldesleukin targets CD122 specific receptors found on the surface of these cancer-killing immune cells, known as CD8+ effector T cells. By first generating antigen-specific cytotoxic T cells with NKTR-262 and then growing these CD8+ effector T cells with bempegaldesleukin, the patient’s entire immunity cycle can potentially be engaged to fight cancer.
In preclinical studies, a single intra-tumoral dose of NKTR-262, administered in combination with bempegaldesleukin, resulted in complete abscopal tumor regressions in multiple mouse syngeneic tumor models.2
About the REVEAL Phase 1/2 Program: NKTR-262 in combination with bempegaldesleukin
REVEAL is a Nektar-sponsored, open-label, multicenter, dose escalation and dose expansion study of NKTR-262 administered as intra-tumoral injections in combination with bempegaldesleukin administered as an IV infusion systemically (doublet). The study also may evaluate the doublet combination with nivolumab (triplet). During the dose escalation phases, recommended Phase 2 dose (RP2D) regimens of the doublet and/or triplet combinations will be established. Following dose escalation, the dose expansion phase will evaluate the doublet and/or triplet combinations in up to 350 patients who have been diagnosed with a range of locally advanced or metastatic cancers including: melanoma, Merkel cell carcinoma, triple-negative breast cancer, renal cell carcinoma, colorectal cancer, squamous cell carcinoma of the head and neck, or sarcoma. For more information, please visit clinicaltrials.gov and search NCT03435640.
References
1Adams S. Toll-like receptor agonists in cancer therapy. Immunotherapy. 2009;1(6):949-964. doi:10.2217/imt.09.70.
2Kivimae, S., et al., Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):P275
2019 ASCO-SITC Clinical Immuno-Oncology Symposium
- Oral presentation/Abstract #28: “Phase Ib: Preliminary clinical activity and immune activation for NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] in patients (pts) with locally advanced or metastatic solid tumors (REVEAL Phase Ib/II Trial).”, Diab, A.
SITC 2018
- Abstract #P364: "Systemic anti-tumor immunity and immune memory formation by a novel TLR7/8 targeting agent NKTR-262 combined with CD122-biased immunostimulatory cytokine NKTR-214", Kivimae, S., et al.
- Abstract #P378: "NKTR-214 (CD122-biased agonist) and NKTR-262 (TLR7/8 agonist) combination treatment pairs local innate immune activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity", Rolig, A., et al.
2018 ESMO Congress
2018 American Association for Cancer Research (AACR) Annual Meeting
- Abstract 2755/Poster 17: “NKTR-262: Prodrug pharmacokinetics in mice, rats, and dogs”
- Abstract 3755/Poster 5: “Comprehensive antitumor immune activation by a novel TLR7/8 targeting agent NKTR-262 combined with CD122-biased immunostimulatory cytokine NKTR-214”
Society for Immunotherapy in Cancer (SITC) 32nd Annual Meeting, National Harbor, MD
- Poster #P275: Harnessing the innate and adaptive immune system to eradicate treated and distant untreated solid tumors, Kivimae, S., et al., Langowski, J., et al.
World Preclinical Congress 2017
- Mar 1, 2019: Nektar Therapeutics Presents Preliminary Immune Activation, Safety and Clinical Activity Data from the Ongoing Dose-Escalation Stage of the REVEAL Study at 2019 ASCO-SITC Meeting
- 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 15, 2018: Nektar Therapeutics Presents New Preclinical Data for its Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting 2018
- Apr 11, 2018: Nektar Announces Dosing of First Patient in Phase 1/2 Clinical Study to Evaluate Combination of TLR Agonist NKTR-262 with CD122-Biased Agonist NKTR-214 in Patients with Advanced Solid Tumors
