On September 13, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported that the first patient has been dosed in the company’s Phase 1a clinical trial of GITRL-Fc (OMP-336B11) (Press release, OncoMed, SEP 13, 2017, View Source [SID1234520507]). GITRL-Fc is an investigational immuno-oncology therapeutic candidate designed to leverage the natural trimeric ligand to modulate the tumor microenvironment by inhibiting T-regulatory cells and activating T-effector cells.
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"The 1st generation immuno-oncology agents, which work by blocking the activation of inhibitory receptors on T cells, have produced impressive results in a number of tumor types," said Kyriakos Papadopoulos, M.D. at South Texas Accelerated Research Therapeutics (START) in San Antonio, TX and a lead investigator for the Phase 1a study. "GITRL-Fc is designed to directly agonize the GITR T cell activation receptor, resulting in increased T-effector cells and a reduction in the number of T-regulatory cells. OncoMed’s agent has demonstrated anti-tumor activity in pre-clinical studies, and as a result, we are excited to initiate this Phase 1a clinical trial of GITRL-Fc."
The Phase 1a open-label clinical trial is designed to assess the safety and tolerability of escalating doses of GITRL-Fc in patients with advanced or metastatic solid tumors. Secondary objectives for the trial include characterization of the pharmacokinetics, immunogenicity and anti-tumor efficacy. Pharmacodynamic and potential predictive biomarkers focused on changes in immune system activation will also be explored. GITRL-Fc will be administered as a single agent every two weeks at escalating dose levels. Once a maximum-tolerated dose has been achieved, an expansion cohort will enroll patients with certain tumor types. The trial will be conducted at five centers in the U.S. and is expected to enroll approximately 30 patients.
"GITRL-Fc is a fusion protein consisting of the fully human natural trimer GITR ligand linked to an Fc. Pre-clinical experiments have suggested that this agent may be a more potent agonist of the GITR trimer receptor than bivalent agonist antibodies," said Robert Stagg, Pharm.D., OncoMed’s Senior Vice President of Clinical Research and Development. "As a result, we are very pleased to have initiated this Phase 1a trial which will help to define the maximum tolerated dose, safety and preliminary efficacy of this immuno-oncology agent."
About GITRL-Fc
GITR (glucocorticoid-induced TNFR-related protein) is a costimulatory molecule that has been shown to be involved in inhibiting the suppressive activity of T-regulatory cells and extending the survival of T-effector cells. Leveraging OncoMed’s proprietary linkerless gene trimer technology, OncoMed has developed a differentiated approach to targeting the GITR/GITRL axis by creating a fusion protein with an Fc-linked fully human trimer ligand that may be more amenable to the natural receptor’s trimeric structure. GITRL-Fc is designed to modulate the tumor microenvironment by inhibiting T-regulatory function and activating T-effector cells. In preclinical studies, a surrogate GITRL-Fc showed superior GITR signaling activation, T-cell proliferation and cytokine production in human T-cell models as compared to two anti-GITR mAbs in competitive development and demonstrated potent in vivo anti-tumor activity. GITRL-Fc is currently being studied in a Phase 1a study in patients with solid tumors. OncoMed is independently developing GITRL-Fc.