Ontuxizumab (MORAb-004)

Ontuxizumab is an investigational monoclonal antibody that recognizes a cell-surface protein, endosialin, also called Tumor Endothelial Marker-1 (TEM1) and CD248, which is expressed on tumor-associated pericytes, tumor stromal cells and directly on a subset of malignant cells. Endosialin is a cell surface protein whose expression is restricted to tumor-associated pericytes. Pericytes play an essential role in new blood vessel formation by supporting endothelial cells and sustaining their differentiation and survival. Tumor-associated pericytes differ from normal pericytes in that they express and appear to depend on the endosialin pathway for their function. Preclinical studies have demonstrated that blockade of the endosialin pathway can suppress PDGFβ-mediated cell growth, while treatment of primary human colorectal tumor organoid cultures results in a pro-immunity microenvironment and associated tumor tissue death.

Ontuxizumab has been investigated as a potential treatment for several types of cancer. A Phase 1 study (NCT00847054) was conducted in collaboration with the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Fox Chase Cancer Center and Memorial Sloan Kettering Cancer Center. Ontuxizumab received U.S. FDA orphan drug designation for sarcoma.  

Based on the Phase 1 study results, multicenter Phase 2 efficacy studies were initiated in melanoma (NCT01335009), sarcoma (NCT01574716) and colorectal cancer (NCT01507545). Analyses and reporting of results from the melanoma and colorectal studies are planned for 2016. Final results for the Phase 2 sarcoma study, which utilized an adaptive design to identify subgroup populations during the study, are planned for 2016.

A Phase 1 study (NCT01773434) of ontuxizumab in Japanese adults with solid tumors has been completed. In collaboration with the Children’s Oncology Group (COG), a Phase 1 study (NCT01748721) in pediatric patients with recurrent or refractory solid tumors or lymphoma completed enrollment.

Current Clinical Studies

MORAb-004-J081-103 Phase 1 Study (Completed)

MORAb-004-J081-103 is a Phase 1 study to evaluate the safety of MORAb-004 in Japanese patients with solid tumors.

For more information and details on this trial, please visit ClinicalTrials.gov. (Indentifier: NCT01773434)

MORAb-004-201-MEL Phase 2 Study (Active; not recruiting)

MORAb-004-201-MEL is a multicenter Phase 2 study in advanced malignant melanoma. The study tests two doses of ontuxizumab as a single agent in patients who have failed other therapies. The goal of the study is to investigate the effect of ontuxizumab on progression-free survival compared to historical control and to identify biomarkers that may serve as an indicator of response to therapy.

For more information visit ClinicalTrials.gov. (Identifier: NCT01335009)

MORAb-004-203-STS Phase 2 Study (Completed)

MORAb-004-203-STS (SOURCE: Sarcoma Study of MORAb-004 Utilization: Research and Clinical Evaluation) is a clinical study that evaluates the safety and efficacy of ontuxizumab when combined with gemcitabine and docetaxel in the treatment of metastatic soft tissue sarcoma. 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 explore the clinical effects of ontuxizumab in the four major subtypes of sarcoma.

For more information and details on this study, please visit ClinicalTrials.gov. (Identifier: NCT01574716)

The information contained herein is investigational and is not intended to make claims of safety or efficacy prior to approval by the FDA or other regulatory authorities. There is no guarantee that the agents described or their uses will be approved by the FDA or other regulatory authorities.