NKTR-262 in combination with NKTR-214

Research Focus: Immuno-oncology

Discovered and wholly owned by Nektar

Unpartnered

Phase 1

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 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

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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.

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

 

2018 American Association for Cancer Research (AACR) Annual Meeting

Society for Immunotherapy in Cancer (SITC) 32nd Annual Meeting, National Harbor, MD

World Preclinical Congress 2017