Morphotek, Inc. announced top-line results from a Phase III study of its investigational agent farletuzumab (MORAb-003) in combination with carboplatin and a taxane in patients with platinum-sensitive epithelial ovarian cancer in first relapse. The study found that farletuzumab in combination with carboplatin and a taxane did not meet the study's primary endpoint of progression-free survival. The post hoc exploratory analysis showed, however, a trend toward improved PFS in some patient subsets and further analysis is ongoing. The preliminary safety analysis indicated that the most commonly reported adverse events were those known to be associated with the study chemotherapy agents. Additionally, some immune-mediated events were observed with farletuzumab. After further analysis of these clinical results, the company will determine a new development strategy based on discussion with external experts and relevant health authorities. In the double-blind, placebo-controlled study, 1,100 patients were enrolled to receive standard-of-care (carboplatin and a taxane [paclitaxel or docetaxel]) chemotherapy and were randomized to three parallel groups to receive one of two different dose levels of farletuzumab or placebo. The Phase III trial, also known as FAR 131, was a randomized, multicenter, double-blind, placebo-controlled study assessing the efficacy and safety of a weekly dose of farletuzumab in combination with standard-of-care (carboplatin and a taxane [paclitaxel or docetaxel]) chemotherapy as assessed by the Response Evaluation Criteria in Solid Tumors in patients with platinum-sensitive ovarian cancer in first relapse. In the study, 1,100 patients at 274 medical centers participated globally. Patients received SOC and were randomized to three parallel groups to receive either 1.25 mg/kg of farletuzumab, 2.5 mg/kg of farletuzumab, or placebo. Patients received SOC every three weeks, and weekly farletuzumab or placebo for approximately six cycles. After approximately six cycles, patients received maintenance of placebo, 1.25 mg/kg or 2.5 mg/kg of farletuzumab until progression. Eligible patients must have been treated initially with surgery, had a response to first-line platinum and taxane-based therapy, and have relapsed as defined by the presence of measurable disease. Patients must have relapsed between six and 24 months from the time of completion of first-line platinum/taxane therapy. They also had to be eligible for carboplatin/taxane treatment.

Morphotek, Inc. announced that the United States Food and Drug Administration (FDA) has granted orphan drug designation to its investigational cancer drug, amatuximab (MORAb-009) for the treatment of malignant pleural mesothelioma, the most common form of mesothelioma, which accounts for around 2,500 cases a year in the United States. This disease affects the pleura, which is the thin balloon shaped lining of the lungs. The Orphan Drug Act (ODA) allows FDA to grant orphan status to a drug which has the potential for the safe and effective treatment, diagnosis, or prevention of a rare disease/disorder that affects fewer than 200,000 people in the United States.(2) Under the ODA, orphan designation qualifies the sponsor of the product for certain incentives, such as tax credits, prescription drug user fee waivers for the development product, and a seven year period of marketing exclusivity from the date of approval. Amatuximab (MORAb-009) is an investigational chimeric IgG1 antibody that targets a cell surface glycoprotein, mesothelin, which is over-expressed in a number of cancers. Mesothelin is thought to be involved in cell adhesion. Its presence is associated with a range of cancers, including pancreatic ductal adenocarcinoma, mesothelioma, epithelial ovarian cancer, and lung adenocarcinoma. Researchers at the National Cancer Institute (NCI) and the Johns Hopkins University have independently validated mesothelin as a potential target of immuno-based therapies.

Morphotek, Inc. 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, or 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 US, 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. 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).