The trial evaluated margetuximab compared with trastuzumab, in combination with chemotherapy, for the treatment of HER 2-positive breast cancer.
Margetuximab, an investigational monoclonal antibody, improved progression-free survival (PFS) when used in combination with chemotherapy in patients with human epidermal growth factor receptor 2- (HER2) positive metastatic breast cancer, according to new data from a pivotal phase 3 trial.
The SOPHIA study, which enrolled 536 patients, evaluated margetuximab in combination with chemotherapy compared with trastuzumab (Herceptin) plus chemotherapy in treating patients with HER2-positive breast cancer.
Margetuximab is designed to target the HER2 oncoprotein, which is expressed by tumor cells in breast, gastroesophageal, and other solid tumors.
In the trial, patients received either margetuximab or trastuzumab in combination with 1 of 4 chemotherapy agents (capecitabine, eribulin, gemcitabine, or vinorelbine). All participants in the trial had previously been treated with trastuzumab and pertuzumab, and approximately 90% had previously received ado-trastuzumab emtansine. According to the findings, patients in the margetuximab arm experienced a 24% reduction in PFS compared with patients treated with trastuzumab (HR=0.76, p=0.033).
Approximately 85% of patients in the study were carriers of the CD16A (FcγRIIIa) 158F allele, which has previously been associated with diminished clinical response to trastuzumab and other antibodies, according to MacroGenics. In this population, patients treated with margetuximab in the study experienced a 32% risk reduction in PFS compared with patients in the trastuzumab arm (HR=0.68, p=0.005).
“There are currently no approved agents for the treatment of patients with metastatic HER2+ breast cancer who have previously received trastuzumab, pertuzumab, and ado-trastuzumab emtansine,” Hope S. Rugo, MD, director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center, said in a press release. “If margetuximab is approved, based on SOPHIA data, I believe that this agent could become a valuable treatment option for these patients.”
Margetuximab plus chemotherapy demonstrated acceptable safety and tolerability, comparable overall to that of trastuzumab and chemotherapy in the study.
Submission of a Biologics License Application to the FDA is anticipated in the second half of 2019, according to the company. MacroGenics is also developing margetuximab to evaluate in combination with anti-PD-1 therapy for the treatment of gastroesophageal cancer.
MacroGenics Announces Positive Results from Pivotal Phase 3 SOPHIA Study of Margetuximab [news release]. MacroGenics. http://ir.macrogenics.com/press-releases. Accessed February 6, 2019.