Morphotek®, Inc. announced today that it has commenced a multi-center, Phase II study evaluating the safety and efficacy of MORAb-004 when combined with gemcitabine and docetaxel in the treatment of metastatic soft tissue sarcoma. MORAb-004 is a monoclonal antibody that specifically binds to endosialin/tumor endothelial marker-1 (TEM-1).
MORAb-004 is thought to function as an inhibitor of the tumor microenvironment. TEM-1 is thought to play a key role in the organization of the tumor cells and support systems (i.e. stroma cells and blood vessels) in most cancer types. Combining a TEM-1 inhibitor such as MORAb-004 with tumor cell targeting agents such as chemotherapy may attack two key parts of the tumor: the tumor cells directly and its supporting structure.
The trial is a randomized, double-blind, placebo-controlled study with a primary endpoint of progression-free survival. Secondary objectives include assessment of an overall survival benefit, identification of biomarkers to predict efficacy, and safety of MORAb-004 in combination with gemcitabine and docetaxel. The trial will use an adaptive design to most efficiently enroll the various subsets of sarcoma.
With this adaptive design, Morphotek expects to enroll up to 200 patients in the study, which is being conducted at clinical centers in the United States, Europe, Australia and New Zealand. As part of the trial, patient tumors and plasma samples will be tested for endosialin/TEM-1 and/or proteins within its pathway to determine if the pattern of expression relates to or determines clinical effect. The goal of these investigations is to identify those patients who had a clinically meaningful response to the combination of MORAb-004 with gemcitabine and docetaxel.
"We are excited to initiate this Phase II study of MORAb-004 in metastatic soft tissue sarcoma, combining MORAb-004 with a standard chemotherapy regimen," stated Christina Coughlin, M.D., Ph.D., Senior Director of Clinical Development at Morphotek. "New agents are needed for the treatment of metastatic soft tissue sarcoma, an orphan disease that remains an area of significant unmet medical need."
MORAb-004 is a humanized monoclonal antibody specific for endosialin/TEM-1 protein. The target is found to be expressed on the cell surface of cells called pericytes that are part of the tumor blood vessel architecture, as well as on fibroblast cells that are part of the tumor stroma. Morphotek obtained exclusive worldwide rights to develop and commercialize this antibody from the Ludwig Institute for Cancer Research (LICR).