Hope S. Rugo
The addition of margetuximab to chemotherapy prolonged PFS compared with trastuzumab plus chemotherapy for patients with HER2-positive metastatic breast cancer, according to phase 3 study results released by the agent’s manufacturer.
Margetuximab (MacroGenics Inc.) is an investigational immune-enhancing monoclonal antibody that targets the HER2 oncoprotein. It is derived from MacroGenics’ proprietary Fc Optimization technology platform and is engineered to enhance engagement of the immune system.
The phase 3 SOPHIA study included 536 patients with HER2-positive metastatic breast cancer treated at approximately 200 sites in North America, Europe and Asia.
All study participants had received trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech), and nearly all (90%) had received the antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla, Genentech).
In the SOPHIA study, patients received either margetuximab or trastuzumab in combination with one of four chemotherapy agents: eribulin, gemcitabine, capecitabine or vinorelbine.
Patients who received margetuximab plus chemotherapy demonstrated a 24% reduced risk for PFS — the study’s primary endpoint — compared with those who received trastuzumab plus chemotherapy (HR = 0.76; P = .033).
Most patients (85%) in the SOPHIA study carried the CD16A (FcyRIIIa) 158F allele, which prior studies suggested is associated with reduced clinical response to trastuzumab and other antibodies.
In SOPHIA, patients with this allele who received margetuximab demonstrated a 32% reduction in risk for PFS compared with those who received trastuzumab (HR = .068; P = .005).
An OS analysis is ongoing.
Full results from the study will be submitted for publication or presentation at a major scientific conference.
“There are currently no approved agents for the treatment of patients with metastatic HER2-positive breast cancer who have previously received trastuzumab, pertuzumab and ado-trastuzumab emtansine. If margetuximab is approved, based on SOPHIA data, I believe that this agent could become a valuable treatment option for these patients,” Hope S. Rugo, MD, director of breast oncology and clinical trials education at UCSF Helen Diller Family Comprehensive Cancer Center, said in a MacroGenics-issued press release.
MacroGenics intends to submit a biologics license application for margetuximab to FDA in the second half of this year.
The company also is developing the antibody in combination with anti-PD-1 therapy for treatment of gastroesophageal cancer.