Second interim overall survival data from phase III SOPHIA study of margetuximab for HER2- positive metastatic breast cancer.-MacroGenics

MacroGenics, Inc. announced topline results from the second pre-specified interim overall survival (OS) analysis for the Phase III SOPHIA study of margetuximab in patients with HER2-positive metastatic breast cancer who have previously been treated with anti-HER2-targeted therapies. Margetuximab is an investigational, immune-enhancing monoclonal antibody derived from the Company�s proprietary Fc Optimization technology platform.

The second interim OS analysis was based on 270 events. In the intent-to-treat (ITT) population, the median OS of patients treated with margetuximab and chemotherapy was prolonged by 1.8 months compared to that of patients who received trastuzumab and chemotherapy (21.6 months versus 19.8 months; hazard ratio [HR]=0.885; 95% CI: 0.693-1.130; p=0.326). A pre-specified exploratory objective was to evaluate the effect of CD16A allelic variation on margetuximab activity. Among the approximately 85% of patients carrying a CD16A 158F allele, the median OS was prolonged by 4.3 months in the margetuximab arm compared to the trastuzumab arm (23.7 months versus 19.4 months; HR=0.793; 95% CI: 0.607-1.035; p=0.087). Among the approximately 15% of patients who were homozygous for the CD16A 158V allele, the trastuzumab arm performed better than the margetuximab arm. The final pre-specified OS analysis is planned after 385 events have accrued, which is projected to occur in 2020.

The first sequential primary endpoint of progression-free survival (PFS) in the ITT population was achieved, with statistical significance as previously reported. Margetuximab plus chemotherapy had a generally comparable safety profile overall to that of trastuzumab plus chemotherapy, consistent with data previously reported from the study. Grade 3 or greater adverse events occurred in 145 (55%) patients on the margetuximab arm compared to 140 (53%) patients on the trastuzumab arm. Serious adverse events occurred in 45 (17%) patients on the margetuximab arm compared to 50 (19%) patients on the trastuzumab arm. Infusion-related reactions were more common with margetuximab treatment than with trastuzumab (13% versus 3%) and were mostly Grade 1 or 2 and associated with the first dose.

Detailed results from the second interim OS analysis from the SOPHIA study are scheduled to be presented during an oral session at the upcoming San Antonio Breast Cancer Symposium (SABCS) in December. MacroGenics expects to submit a Biologics License Application (BLA) to the FDA before the end of 2019.