Macrogenics, Inc. Announces the Publication of Results from the Sophia Trial of Margenza
January 25, 2021 at 07:30 am
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MacroGenics, Inc. announced the publication of results from the SOPHIA trial of MARGENZA™ (margetuximab-cmkb) in the Journal of the American Medical Association (JAMA) Oncology. SOPHIA is a pivotal Phase 3 clinical trial of 536 adult patients with metastatic HER2-positive breast cancer previously treated with two or more anti-HER2 regimens and from one to three lines of therapy for metastatic disease. In the study, MARGENZA demonstrated a statistically significant 24% reduction in the risk of disease progression or death compared to Herceptin, each in combination with chemotherapy (Hazard Ratio [HR] = 0.76; 95% CI, 0.59-0.98; p=0.03; median PFS 5.8 vs. 4.9 months). In addition to the statistically significant improvement in primary endpoint of PFS by centrally blinded review, investigator-assessed PFS (based on 337 events) was also greater with MARGENZA compared to trastuzumab with a 30% PFS relative risk reduction compared to trastuzumab (HR=0.70; 95% CI, 0.56-0.87; P=0.001; median investigator-assessed PFS 5.6 vs 4.2 months). Among 524 response-evaluable patients, the objective response rates for MARGENZA plus chemotherapy and trastuzumab plus chemotherapy were 22% and 16%, respectively (P=0.06) and the clinical benefit rates were 37% for MARGENZA and 25% for trastuzumab, (P=0.003). At the prespecified interim Overall Survival (OS) analysis, based on 270 events, median OS was 21.6 months with MARGENZA and 19.8 months with trastuzumab (HR=0.89; 95% CI, 0.69-1.13; P=0.33). The stopping threshold was not reached. The final OS analysis will occur after 385 events, and it is expected in the second half of 2021. Adverse reactions occurring in greater than twenty percent of patients with MARGENZA in combination with chemotherapy were fatigue/asthenia (57%), nausea (33%), diarrhea (25%), and vomiting (21%). The MARGENZA U.S. Prescribing Information has a BOXED WARNING for left ventricular dysfunction and embryo-fetal toxicity. In addition, MARGENZA can cause infusion related reactions (IRRs). IRRs occurred in 13% of patients treated with MARGENZA, with the majority reported as Grade 2 or less. Grade 3 IRRs occurred in 1.5% of patients.
MacroGenics, Inc. is a biopharmaceutical company focused on developing and commercializing monoclonal antibody-based therapeutics for the treatment of cancer. It generates its pipeline of product candidates primarily from its suite of antibody-based technology platforms, which have applicability across broad therapeutic domains. It is developing product candidates that target various tumor-associated antigens and immune checkpoint molecules. Its lead pipeline program is vobramitamab duocarmazine (vobra duo), an antibody-drug conjugate (ADC) that targets B7-H3, a molecule in the B7 family of immune regulator proteins that is expressed by several different tumor types. Its clinical pipeline includes two product candidates based on its, bispecific DART technology that co-engages both PD-1 and other checkpoint molecules. These candidates include lorigerlimab and tebotelimab. In addition, it is developing MGD024, a bispecific DART molecule. It is also developing various other programs.
MACROGENICS, INC. 
