US-based OncoMed Pharmaceuticals has begun dosing patients in a Phase Ia clinical trial of its therapeutic candidate GITRL-Fc (OMP-336B11) to treat patients suffering from solid tumours.
Based on the firm’s linkerless gene trimer technology, GITRL-Fc is an investigational immuno-oncology agent being developed to utilise the natural trimeric ligand to inhibit T-regulatory cells and stimulate T-effector cells for altering the tumour microenvironment.
The therapeutic candidate is designed to directly agonise the glucocorticoid-induced TNFR-related protein (GITR) T-cell activation receptor, which leads to decreased T-regulatory cells and increased T-effector cells.
Set to be conducted at five sites in the country, the open-label Phase Ia trial will evaluate the safety and tolerability of increasing GITRL-Fc doses in 30 advanced or metastatic solid tumour patients.
OncoMed Pharmaceuticals clinical research and development senior vice-president Robert Stagg said: "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.”
The trial’s secondary objectives are pharmacokinetics, immunogenicity and anti-tumour efficacy, while pharmacodynamic and potential predictive biomarkers of changes in immune system activation will also be investigated.
GITRL-Fc will be assessed as a monotherapy, given every two weeks at escalating dose levels.
Upon determination of a maximum-tolerated dose, an expansion cohort will be initiated for patients with specific types of tumours.