NKTR-262 in combination with NKTR-214
Research Focus: Immuno-oncology
Discovered and wholly owned by Nektar
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 NKTR-214 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 NKTR-214, the patient’s entire immunity cycle can potentially be engaged to fight cancer.
In preclinical studies, a single intratumoral dose of NKTR-262, administered in combination with NKTR-214, 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 NKTR-214
REVEAL is a Nektar-sponsored, open-label, multicenter, dose escalation and dose expansion study of NKTR-262 administered as intratumoral injections in combination with NKTR-214 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, ovarian cancer, renal cell carcinoma, colorectal cancer, urothelial carcinoma, or sarcoma. For more information, please visit clinicaltrials.gov and search NCT03435640.
1Adams S. Toll-like receptor agonists in cancer therapy. Immunotherapy. 2009;1(6):949-964. doi:10.2217/imt.09.70.
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.
- 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
- Poster 446TIP: “REVEAL: A phase 1/2, open-label, multicenter, dose escalation and dose expansion study of NKTR-262 [TLR 7/8 agonist] plus NKTR-214 [CD122-biased agonist] with or without nivolumab (nivo) in patients (pts) with locally advanced or metastatic solid tumor malignancies”, Diab, A., et al.
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