Mark D. Pegram, MD
The Fc-modified monoclonal antibody margetuximab in combination with chemotherapy may offer a new treatment option for patients with HER2-positive metastatic breast cancer.
during the 2016 San Antonio Breast Cancer Symposium, Mark D. Pegram, MD, director of the Breast Cancer Oncology Program at Stanford Medicine, provided an overview of the SOPHIA trial and the continued need to advance treatment in HER2-positive breast cancer.
OncLive: Please discuss the SOPHIA trial.
: SOPHIA is a randomized phase III pivotal registration trial exploring a new Fc domain-engineered antibody called margetuximab. It binds to the same epitope as does trastuzumab. However, it has enhanced immune-effector function. In other words, the Fc domain of margetuximab is engineered so that it has higher binding affinity for activating Fc gamma receptors on human immune-effector cells and lower binding affinity to some of the decoy negative regulatory receptors on those same cells.
The primary endpoints are progression-free survival and overall survival. Patients with brain metastases—if they are previously treated and stable—are allowed to enroll, so that is not an absolute exclusion criteria. It is a fairly liberal eligibility and exclusion criteria. It is an important study that will test the hypothesis of whether you can go 1 above and beat trastuzumab. Starting in the salvage setting—if that’s a positive trial—there will no doubt be a great interest to move up further in earlier lines.
Are there earlier findings with this drug that demonstrate the rationale for the phase III trial?
Absolutely. There was a phase I dose-escalation study of margetuximab presented at ASCO a couple of years ago. It was quite exciting because heavily pretreated HER2-positive solid tumors had responses even during dose escalation with a single agent. One of the patients had HER2-positive breast cancer with prior progression—even after T-DM1—and still had an objective clinical response to single-agent margetuximab. It is anecdotal evidence so far, but it’s pretty promising. That really bodes well for the outcome of the phase III trial.
What is the unmet need for a trial such as this one?
There is still a high unmet need in metastatic HER2-positive disease. Sadly, despite our best efforts and a plethora of very active agents—which have indeed improved overall survival significantly—they have not absolutely resulted in cures, except for the rare exceptional responders that we occasionally see.
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