On December 19, 2019 MacroGenics, Inc. (Nasdaq: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that the Company has submitted a Biologics License Application (BLA) for margetuximab, an investigational, Fc-engineered, monoclonal antibody that targets HER2 (Press release, MacroGenics, DEC 19, 2019, View Source [SID1234553174]). The margetuximab BLA is for the treatment of patients with metastatic HER2-positive breast cancer in combination with chemotherapy. The submission is based on the safety and efficacy results of the pivotal phase 3 SOPHIA study, which were first presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, with updated data recently presented at the 2019 San Antonio Breast Cancer Symposium.

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"As the Company’s first BLA submission, this is a key milestone for MacroGenics. We are grateful to the patients who participated in this study, as well as their families, and all involved in developing margetuximab," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "With this submission, we look forward to working with the Agency to bring margetuximab to appropriate patients. We believe the positive clinical trial results in SOPHIA demonstrate margetuximab’s potential as a treatment option for patients living with this devastating disease."

About the SOPHIA Study

The SOPHIA study (NCT02492711) is a randomized, open-label Phase 3 clinical trial evaluating margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer, who have previously been treated with anti-HER2-targeted therapies. All study patients had previously received trastuzumab and pertuzumab, and approximately 90% had previously received ado-trastuzumab emtansine, or T-DM1.

The study enrolled 536 patients who were randomized 1:1 to receive either margetuximab (n=266) given intravenously at 15 mg/kg every three weeks or trastuzumab (n=270) given intravenously at 6 mg/kg (or 8 mg/kg for loading dose) every three weeks in combination with one of four chemotherapy agents (capecitabine, eribulin, gemcitabine or vinorelbine) given at the standard dose. Intent-to-treat PFS analysis occurred after 265 PFS events, and the first and second interim OS analyses occurred after 158 and 270 OS events, respectively. Final OS analysis is planned after 385 events and is expected to occur in the second half of 2020.

Primary endpoints are sequentially-assessed PFS, determined by centrally-blinded radiological review, and OS. Key secondary endpoints are PFS by investigator assessment and ORR. Tertiary endpoints include ORR by investigator assessment and safety. PFS and ORR were assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Effect of CD16A (FcγRIIIa) 158 genotype on margetuximab activity is a pre-specified exploratory endpoint.

About Margetuximab

Margetuximab is an investigational monoclonal antibody that targets the HER2 oncoprotein. Margetuximab was designed to provide HER2 blockade and has similar HER2 binding and antiproliferative effects as trastuzumab. In addition, the Fc region of margetuximab has been engineered to enhance the engagement of the immune system. Margetuximab is also being evaluated in combination with anti-PD-1 therapy for the potential treatment of patients with HER2-positive gastric or gastroesophageal junction cancer. MacroGenics has initiated the Phase 2/3 MAHOGANY study (NCT04082364). For more information, please visit www.clinicaltrials.gov.