Amatuximab (MORAb-009) is an investigational, chimeric, IgG1 antibody that targets a cell-surface glycoprotein, mesothelin, which is over-expressed on 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 Johns Hopkins University independently validated mesothelin as a potential target of immunobased therapies.
Amatuximab has been investigated as a monoclonal antibody for potential treatment of mesothelioma. An Investigational New Drug application was opened for MORAb-009 in 2006. A Phase 1 study (NCT00325494) in patients with mesothelin-positive cancers (pancreatic, ovarian, mesothelioma and lung) was conducted at Johns Hopkins, Fox Chase Cancer Center and the National Cancer Institute. A separate Phase 1 study (NCT01018784) was also conducted in patients of Japanese origin.
A global, single-arm, open-label, Phase 2 study (NCT00738582) was conducted to test whether amatuximab plus standard of care could improve progression-free survival in patients with newly diagnosed, unresectable, malignant pleural mesothelioma (MPM). Secondary endpoints included overall response, overall survival and safety. Results of the study showed that amatuximab failed to statistically improve progression-free survival in the intent-to-treat population compared to historic controls; however, the 14.8-month median overall survival and 39% objective response rate compared favorably to the historical control of 13.3 months and 21%, respectively. These results, along with exposure-response modeling, suggested further investigation was warranted; therefore, a randomized, double-blind, placebo-controlled, Phase 2 trial (ARTEMIS; NCT02357147) was initiated to determine if amatuximab improves the overall survival of unresectable, previously untreated, MPM patients. All patients received the standard-of-care chemotherapy regimen for four to six cycles combined with either amatuximab or placebo, followed by maintenance therapy with either amatuximab or placebo. Secondary objectives include evaluating progression-free survival, objective response rate, duration of response, disease control and performance status maintenance, disease control rate, health-related quality of life, and safety.
Amatuximab received orphan drug designation for MPM.
Current Clinical Studies
MORAb-009-201 Phase 2 First-line Mesothelioma (Active; not recruiting)
A Study of the Safety and Efficacy of Amatuximab in Combination with Pemetrexed and Cisplatin in Subjects with Unresectable Malignant Pleural Mesothelioma (MPM) (ARTEMIS).
For more information visit ClinicalTrials.gov. (Identifier: NCT02357147)
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.