The U.S. Food and Drug Administration (FDA) has granted fast track designation to the investigation of motolimod (VTX-2337) when administered in combination with pegylated liposomal doxorubicin for the treatment of women with ovarian cancer whose disease has progressed on or recurred after platinum-based chemotherapy.
Motolimid is a novel Toll-like Receptor 8 (TLR8) immunotherapy currently being evaluated in two randomized, placebo-controlled phase II trials. The agent directly activates multiple components of the innate immune system, including human myeloid dendritic cells, monocytes, and natural killer cells, which results in the production of high levels of mediators known to orchestrate the integration of innate and adaptive antitumor responses.
Clinical Trials Underway
Results from preclinical models suggest that combining motolimod with pegylated liposomal doxorubicin may provide a synergistic effect in stimulating a variety of immune pathways associated with antitumor activity. A recently completed phase I trial in this same study population demonstrated that the combination was safe and well-tolerated.
VentiRx has completed enrollment of over 290 patients in the GOG-3003 randomized, placebo-controlled phase II trial of motolimod in combination with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer for whom prior platinum-based chemotherapy has failed. The primary endpoint of the study is overall survival. In April 2014, the FDA granted Orphan Drug designation to motolimod for the treatment of ovarian cancer.
GOG-3003 is one of two phase II clinical trials of motolimod currently underway. The second trial, called Active8, is a company-sponsored, randomized, phase II placebo-controlled trial in patients with locally advanced and metastatic squamous cell carcinoma of the head and neck. ■