The Phase III SOPHIA clinical trial is evaluating  whether margetuximab (MacroGenics) plus chemotherapy has longer progression free survival and overall survival than patients treated with trastuzumab (Herceptin/Roche) plus chemotherapy. Dr. Hope S. Rugo of University of California, San Francisco, offers some updates for this study addressing patients with HER2-positive metastatic breast cancer who have received prior anti-HER2 therapies.

The Study

The SOPHIA study’s purpose is to determine whether patients treated with margetuximab plus chemotherapy have longer progression free survival and overall survival than patients treated with trastuzumab plus chemotherapy for patients with HER2-positive metastatic breast cancer who have received prior anti-HER2 therapies. The study commenced in 2015 and runs through March 2021. About 194 research sites are involved; Dr. Rugo from University of California, San Francisco, represents one of the participating investigators. She recently presented the updated findings at the 2019 San Antonio Breast Cancer Symposium. She was interviewed recently on Onclive

The Updates

Dr. Rugo reported that the SOPHIA investigators presented about one year’s worth of follow up data at the San Antonio conference this year with an emphasis on progression-free survival by investigator assessment. They do not have the central blinded analysis as of yet.

Margetuximab resulted in a significant improvement for progression-free survival compared to trastuzumab with a P value that is improved to .0006—Rugo labels this “highly significant” and a “very good hazard ratio” with a 24% relative improvement. The “absolute difference” between the two drugs was 1.3 months, which she clarifies is small, but Rugo again emphasized the P value and hazard ratio “are very important” in terms of assessing the benefit of margetuximab versus trastuzumab.

Dr. Rugo reports that when looking at “response” the results were significantly increased with margetuximab as was the clinical benefit rate—Rugo reiterated a big and clinically important difference in response. They looked at a second interim analysis of overall survival. Now with 70% of planned events and with this analysis, there is a “non-significant” trends towards improved survival with margetuximab

What is Margetuximab?

The experimental drug is a chimeric IgC monoclonal antibody against HER2 designed for the treatment of cancer. The drug was initially created by Raven biotechnologies—later acquired by current sponsor MacroGenics. It was engineered to increase affinity for CD16A polymorphisms and decrease affinity for FcyRIIB (CD32B), an inhibitory receptor. It binds to the same target (epitope) as trastuzumab, on the HER2 receptor.

It is currently in Phase III clinical trials for combination therapy in metastatic breast cancer in collaboration with Merck.

Lead Research/Investigator

Dr. Hope S. Rugo, University of California, San Francisco

Source: ClinicalTrials.gov

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