MacroGenics announced that the first patient has been dosed in the Phase 2/3 MAHOGANY clinical trial of margetuximab, an investigational, Fc-optimized monoclonal antibody targeting HER2, in combination with a checkpoint inhibitor, with or without chemotherapy, as a potential first-line treatment for patients with HER2-positive gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.
“The MAHOGANY study for patients with gastric or gastroesophageal junction cancer is designed to support registration of margetuximab and is a part of our strategy to advance margetuximab in HER2-positive cancers,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. “The combination of margetuximab and a checkpoint inhibitor could potentially provide a chemotherapy-free option as a first-line treatment for patients whose tumors are positive for both HER2 and PD-L1 or be used with chemotherapy in a broader HER2-positive population to improve the clinical activity of existing standard of care.”
The MAHOGANY Study Design
MAHOGANY (NCT04082364) is a Phase 2/3 clinical trial in two modules designed to evaluate margetuximab in combination with a checkpoint inhibitor, with or without chemotherapy, as a potential first-line treatment for patients with advanced or metastatic HER2-positive GEJ/GC.
Module A is designed as a single arm study to test margetuximab plus MGA012 (also known as INCMGA00012), an investigational anti PD-1 monoclonal antibody, in patients with HER2-positive and PD-L1-positive tumors. The primary outcome measure for efficacy is objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST).
Module B is designed as a randomized trial to test margetuximab plus a checkpoint inhibitor in combination with chemotherapy compared to standard of care therapy of trastuzumab with chemotherapy in patients with HER2-positive tumors irrespective of PD-L1 expression. Patients randomized to one of two experimental arms containing a checkpoint inhibitor will receive either MGA012 or MGD013, an investigational DART® molecule targeting PD-1 and LAG-3. The primary outcome measure for efficacy is overall survival (OS).
The Phase 2/3 clinical trial is planned to be conducted at clinical sites globally, in collaboration with Zai Lab, the company’s regional partner in Greater China.
The MAHOGANY study is based on results from an ongoing Phase 2 study of margetuximab plus pembrolizumab, an anti-PD-1 monoclonal antibody, for patients with advanced HER2-positive GC or GEJ cancer who have previously been treated with chemotherapy and trastuzumab in the metastatic setting. Data were presented at the European Society for Medical Oncology (ESMO) Annual Congress in September 2019.
Source: Company Press Release