Margetuximab Helps to Delay Disease Progression in Advanced, HER2-positive Breast Cancers, Phase 3 Trial Shows

Margetuximab Helps to Delay Disease Progression in Advanced, HER2-positive Breast Cancers, Phase 3 Trial Shows

A combination of MacroGenics‘ HER2 antibody margetuximab and standard chemotherapy is superior to Herceptin (trastuzumab) plus chemotherapy at extending the time to disease progression among advanced and pre-treated breast cancer patients whose tumors are positive for HER2 (human epidermal growth factor receptor 2), a Phase 3 trial shows.

Specifically, the SOPHIA trial (NCT02492711) included breast cancer patients who had received at least two prior HER2-targeted treatments for their metastatic disease —including Genentech‘s Herceptin, Perjeta (pertuzumab), and Kadcycla (ado-trastuzumab emtansine) — but no more than three prior treatments in total.

“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, Breast Oncology and Clinical Trials Education, 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.”

Treatment for HER2-positive breast cancer normally includes HER2-targeted therapies. Herceptin and Perjeta are two antibodies that directly target the HER2 protein, working to stop its pro-tumor activities and to induce strong immune responses against cancer cells. Kadcycla is made of Herceptin’s antibody bound to a cytotoxic compound, and is designed to enter and kill cancer cells once the antibody binds to HER2.

While these approaches have significantly improved the survival outcomes of HER2-positive breast cancer patients, some still see their disease return. In these cases, it is likely that the cancer will respond poorly to additional HER2-targeted treatments.

Margetuximab is also an HER2-targeting antibody, but designed in a manner that increases immune system responses. MacroGenics believes it could improve the outcomes of patients who have already used multiple HER2-targeted treatments.

SOPHIA included 536 patients across nearly 200 sites in North America, Europe, and Asia. It assigned patients to received either margetuximab or Herceptin, given along with standard chemotherapy — capecitabine, eribulin, gemcitabine, or vinorelbine.

Its main objectives were to determine if margetuximab was better than Herceptin at delaying disease progression or death, at extending survival, and whether it caused fewer severe infusion-related reactions. Secondary measures include objective response rate, and incidence of infusion-related reactions of any grade.

In the trial, all patients were previously treated with Herceptin and Perjeta for their metastatic breast cancer. Kadcycla had also been given to 90% of patients.

SOPHIA met its primary goal of progression-free survival, with margetuximab reducing the risk of disease progression or death by 24% compared to Herceptin. Interestingly, in a population that is usually defined by poor responses to Herceptin and other antibodies — those with the CD16A (FcγRIIIa) 158F variation — the risk was reduced by 32%, researchers reported.

Researchers are now preparing the data for publication and for presentation at a major scientific meeting. Overall survival data will be assessed in a follow-up analysis, as recommended by the trial’s independent Data Safety Monitoring Committee.

MacroGenics expects to request margetuximab’s approval with the U.S. Food and Drug Administration in the second half of 2019.

“We are pleased with the SOPHIA clinical results and are especially grateful to the patients, their caregivers, trial investigators and site personnel who participated in the study,” said Scott Koenig, MD, PhD, MacroGenics’ president and CEO.