“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
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
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 (
About Gastric and Gastroesophageal Junction Cancer
Cancer of the stomach (gastric cancer) or the gastroesophageal junction (where the esophagus joins the stomach) is collectively known as gastroesophageal adenocarcinoma and is the fifth most common tumor type worldwide. Both GC and GEJ cancer are often diagnosed at an advanced stage and therefore have very poor prognosis, with a 5-year survival of 5-20%. Chemotherapy is the standard of care for first-line therapy and may be combined with trastuzumab for the approximately 20% of patients whose tumors are HER2-positive.
Margetuximab is an investigational monoclonal antibody that targets the HER2 oncoprotein. HER2 is expressed by tumor cells in breast, gastroesophageal and other solid tumors. Margetuximab was designed to provide HER2 blockade and has similar HER2 binding and antiproliferative effects as trastuzumab. In addition, margetuximab has been engineered with MacroGenics’ Fc Optimization technology to enhance the engagement of the immune system and affect killing of cancer cells through antibody dependent cellular cytotoxicity (ADCC). Beyond gastric and GEJ cancer, margetuximab is also being evaluated in combination with chemotherapy in the Phase 3 SOPHIA study for the treatment of patients with metastatic HER2-positive breast cancer who have previously been treated with anti-HER2-targeted therapies.
MGA012 is an investigational, humanized, proprietary anti-PD-1 monoclonal antibody being developed for use as monotherapy as well as in combination with other potential cancer therapeutics. MGA012 was licensed to
MGD013 is an investigational, first-in-class bispecific DART molecule designed to provide co-blockade of PD-1 and LAG-3 for the potential treatment of a range of solid tumors and hematological malignancies.
Cautionary Note on Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company's strategy, future operations, clinical development of the Company's therapeutic candidates, milestone or opt-in payments from the Company's collaborators, the Company's anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words "subject to", "believe", "anticipate", "plan", "expect", "intend", "estimate", "project", "may", "will", "should", "would", "could", "can", the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for regulatory approvals, other matters that could affect the availability or commercial potential of the Company's product candidates and other risks described in the Company's filings with the
Anna Krassowska, Ph.D., Vice President, Investor Relations & Corporate Communications Jim Karrels, Senior Vice President, CFO 1-301-251-5172, email@example.com
Source: MacroGenics, Inc.