Nektar begins 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

Nektar Therapeutics (Nasdaq: NKTR) today announced that it has initiated dosing patients in the Phase 1/2 REVEAL clinical study evaluating the efficacy and safety of the combination of investigational medicines NKTR-262 and NKTR-214 in the treatment of solid tumors.  NKTR-262 is a novel toll-like receptor (TLR) agonist designed to induce the body's innate immune response and create antigen-specific T cells to fight cancer. NKTR-214 is designed to activate the adaptive immune system to expand and proliferate these specific cancer-fighting T cells in the tumor micro-environment.

"The REVEAL study is intended to show the synergistic impact on the entire immune activation cascade of an initial intratumoral injection of NKTR-262 followed by treatment with NKTR-214," said Mary Tagliaferri, M.D., Senior Vice President of Clinical Development and Chief Medical Officer at Nektar Therapeutics. "Engagement of the innate and adaptive immune cascades is the most effective way to restore immune surveillance mechanisms to drive both local tumor antigen production and a specific and sustained T cell response to attack a patient's tumors.  We believe the combination approach of these two novel immuno-oncology agents could ultimately help patients with many types of advanced or metastatic solid tumor cancers, including those resistant to existing immunotherapies."

The combination therapy has been successful in animal models. 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.

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.2 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.  

Nektar currently has a number of molecules in development. These include a new opioid pain treatment designed to avoid abuse potential, various cancer treatments, and a drug for systemic lupus erythematosus,