On October 7, 2015 Nektar Therapeutics (NASDAQ:NKTR) reported that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for NKTR-214, its lead immuno-oncology candidate. NKTR-214 is a CD122-biased immune-stimulatory cytokine that is designed to stimulate the patient’s own immune system to destroy cancer cells (Press release, Nektar Therapeutics, OCT 7, 2015, View Source [SID:1234507662]). Schedule your 30 min Free 1stOncology Demo! The company plans to initiate a Phase 1/2 clinical study by the end of 2015. The study will evaluate the safety, tolerability and efficacy of NKTR-214 in patients with solid tumor malignancies and will include expansion cohorts that will evaluate NKTR-214 both as a single-agent and in combination with a checkpoint inhibitor.
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"As a new cytokine with biased receptor activity and an antibody-like dosing schedule, NKTR-214 could emerge as a differentiated immuno-oncology therapy that specifically stimulates T-cell growth to fight cancer," said Stephen Doberstein, PhD, Senior Vice President and Chief Scientific Officer of Nektar. "In preclinical studies with NKTR-214, we not only observed single-agent efficacy in multiple tumor models, but when administered in combination with a checkpoint inhibitor, we see a dramatic immune-educating vaccine-like effect with NKTR-214. We are excited to start our first-in-human study and we expect to have initial data from the dose-escalation phase of the trial by the second half of 2016."
The Phase 1/2 clinical program will be conducted at multiple clinical sites including MD Anderson Cancer Center and Yale Cancer Center. In addition to the Phase 1/2 clinical program, Nektar and MD Anderson will conduct translational research to identify predictive biomarkers that can be used in the future development of NKTR-214.
About NKTR-214
NKTR-214 is a CD122-biased immune-stimulatory cytokine that is designed to preferentially stimulate the expansion and maintenance of CD8-positive effector T cells, which are tumor-killing cells found naturally in the body. CD122, which is also known as the Interleukin-2 (IL-2) receptor beta subunit, is a key signaling receptor that is known to increase the proliferation of CD8-positive effector T cells.1 These tumor-killing cells comprise a key component of the tumor infiltrating lymphocytes that provide cell-mediated anti-tumor effects.1 By biasing activation to the CD122 receptor, NKTR-214 enhances the generation of CD8-positive T cells in the tumor.
In preclinical studies, a single dose of NKTR-214 resulted in an approximate 400-fold AUC exposure within the tumor compared with an equivalent dose of aldesleukin, an existing IL-2 therapy. This increase potentially enables, for the first time, an antibody-like dosing regimen for a cytokine.2
At the Inaugural CRI-CIMT-EATI-AACR Immunotherapy Conference in New York in September 2015, Nektar presented data demonstrating that NKTR-214 induces durable and specific anti-tumor immunity as a single agent and when combined with checkpoint inhibitors in preclinical models. As a single agent, NKTR-214 demonstrated efficacy in multiple preclinical models. In combination with either anti-CTLA4 or anti-PD-1 checkpoint inhibitor therapies, NKTR-214 produced durable anti-tumor immunotherapeutic effects, which persisted long after the termination of dosing. In a preclinical tumor re-challenge study, sequential dosing of anti-CTLA-4 followed by NKTR-214 resulted in durable and complete responses. At 142 days following the final dose, with no additional treatment, the complete responders demonstrated sustained resistance to multiple tumor re-challenges. In highly-resistant established melanoma tumor models, treatment with NKTR-214 resulted in a controlled, sustained and biased T-cell activating signal and a mean ratio of CD8-positive T cells to CD4-positive regulatory T-cells (which can suppress tumor killing) of 450:1 in the tumor infiltrating lympho