Nektar Therapeutics announced that it has entered into a new clinical study collaboration with Cellular Biomedicine Group Inc. ("CBMG"). The study will evaluate Nektar's NKTR-255, a novel interleukin-15 (IL-15) receptor agonist, in combination with CBMG's C-TIL051, a tumor-infiltrating lymphocyte (TIL) therapy, in advanced non-small cell lung cancer (NSCLC) patients that are relapsed or refractory to anti-PD-1 therapy. NKTR-255 is a novel polymer-conjugated human IL-15 receptor agonist currently being studied in two separate Phase 2 studies in combination with cell therapies and immunotherapies. Preclinical and early clinical data suggest that IL-15 can improve proliferation and persistence of cellular therapies including TIL, TCR, and CAR-T therapies to increase specific anti-tumor activity. C-TIL051 is an autologous adoptive cell therapy being developed by CBMG that is comprised of a patient's ex vivo expanded lymphocytes using CBMG's proprietary manufacturing process. The development of C-TIL051 was based on initial NSCLC TIL studies demonstrating encouraging safety and efficacy results (NCT03215810, NCT03645928). In October of last year, CBMG received clearance of an Investigational New Drug (IND) application for C-TIL051 for late-stage NSCLC patients that are relapsed or refractory to anti-PD-1 therapy. Under the new collaboration, CBMG will add NKTR-255 to its ongoing CBMG-sponsored Phase 1 clinical trial evaluating C-TIL051 in NSCLC patients who have relapsed on or were refractory to anti-PD-1 therapy, which is being conducted at Duke Cancer Institute (NCT05676749). The study is expected to enroll a total of 20 patients. Nektar will contribute NKTR-255 supply for the study. Nektar and CBMG will each maintain existing global rights to their respective investigational medicines.
NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body's innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response. Preclinical and early clinical findings suggest IL-15 can improve proliferation and persistence of cellular therapies including TIL, TCR, and CAR-T therapies to increase specific anti-tumor activity. NKTR-255 is currently being studied in two separate Phase 2 studies in combination with cell therapies and immunotherapy. A Phase 2/3 study is underway that combines NKTR-255 with approved CAR-T cell therapies in patients with diffuse large B-cell lymphoma, which is currently recruiting (NCT05664217). NKTR-255 is also being studied in a Phase 2 study in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma in the Merck KGaA-sponsored JAVELIN Bladder Medley trial (NCT05327530), as well as in combination with durvalumab in patients with locally advanced NSCLC in an IST conducted at M.D. Anderson Cancer Center. In addition, there are two ongoing investigator sponsored trials (ISTs) evaluating NKTR-255 as adjunct therapy following a CAR-T cell therapy. Fred Hutchinson Cancer Center is conducting a Phase 1 study evaluating NKTR-255 following lisocabtagene maraleucel treatment in patients with relapsed/refractory large B-cell lymphoma (NCT05359211), and Stanford University is conducting a Phase 1 study evaluating NKTR-255 following an investigational CD19/22 CAR-T cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (NCT03233854).