Phase III SOPHIA study with MGAH 22 not yet statistically significant in metastatic breast cancer.- MacroGenics

MacroGenics presented updated results from the Phase III SOPHIA study comparing MGAH 22 (margetuximab) plus chemotherapy versus trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer who have previously been treated with anti-HER2-targeted therapies. Overall survival (OS) results favored margetuximab plus chemotherapy compared with trastuzumab and chemotherapy in the intention-to-treat (ITT) population; however, these data did not reach statistical significance at this second interim analysis as of a September 2019 cut-off after 270 events (median OS=21.6 months versus 19.8 months; hazard ratio [HR]=0.89; 95% CI: 0.69-1.13; P=0.326). The final pre-specified OS analysis is planned after 385 events have accrued, which is projected to occur in the second half of 2020.

A pre-specified exploratory objective of the study was to evaluate the effect of CD16A (Fc? receptor) allelic variation on margetuximab activity. Among the genetically defined subpopulation of patients carrying a CD16A 158F allele, who represent approximately 85% of the human (and SOPHIA study) population, the median OS at the second interim analysis was prolonged by 4.3 months in the margetuximab arm compared to the trastuzumab arm (23.7 months versus 19.4 months; HR=0.79; 95% CI: 0.61-1.04; nominal 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.

As previously reported, margetuximab plus chemotherapy showed a statistically significant improvement in independently-assessed progression-free survival (PFS) compared to trastuzumab plus chemotherapy in this study as of an October 2018 cut-off after 256 events (median PFS=5.8 months versus 4.9 months; HR=0.76; 95% CI: 0.59-0.98; P=0.033). An updated investigator-assessed analysis as of a September 2019 cut-off showed consistent results after 430 PFS events (median PFS=5.7 months in the margetuximab arm versus 4.4 in the trastuzumab arm; HR=0.71; nominal P=0.0006). Similarly, at the time of this updated analysis, additional patients were evaluable for response in the ITT population. Investigator-assessed objective response rate (ORR) was 25.2% (95% CI: 20.1-30.9%) in the margetuximab arm compared to 13.7% (95% CI: 9.8�18.4%) in the trastuzumab (nominal P=0.0006). The clinical benefit rate (CBR, which includes CR+PR+SD>6 months, was 48.1% (95% CI: 42.0-54.3%) in the margetuximab arm versus 35.6% (95% CI: 29.9-41.6%) in the trastuzumab arm (nominal P=0.0025).

Margetuximab plus chemotherapy has shown a safety profile generally comparable to that of trastuzumab plus chemotherapy in this study. As of the April 2019 cut-off for safety, Grade 3 or greater adverse events occurred in 142 (54%) patients on the margetuximab arm compared to 140 (53%) patients on the trastuzumab arm. The data were presented today during an oral session at the San Antonio Breast Cancer Symposium.