Margetuximab is a chimeric IgG monoclonal antibody against HER2 designed for the treatment of cancer.
It binds to the same target as trastuzumab, on the HER2 receptor.
Approved in combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2 regimens, at least 1 of which was for metastatic disease.
Tradename Margenza.
The approval was based on safety and efficacy results observed in the pivotal, randomized, open-label, phase 3 SOPHIA trial
The trial compared margetuximab-cmkb plus chemotherapy to trastuzumab (Herceptin) plus chemotherapy in patients with HER2-positive metastatic breast cancer who had previously been treated with anti-HER2-targeted therapies.
The study demonstrated a statistically significant 24% reduction in the risk of disease progression or death with margetuximab-cmkb plus chemotherapy compared with trastuzumab plus chemotherapy, with a median progression-free survival 5.8 vs 4.9 months.
The objective response rate for margetuximab-cmkb plus chemotherapy was 22% and 16% for trastuzumab plus chemotherapy.
It is only HER2-targeted agent to have shown a PFS improvement versus trastuzumab in a head-to-head Phase 3 clinical trial.
A total of 536 patients were randomized 1:1 to receive either margetuximab-cmkb (n = 266) given intravenously at a dose of 15 mg/kg every 3 weeks or trastuzumab (n = 270) given intravenously at a dose of 6 mg/kg (or 8 mg/kg for loading dose) every 3 weeks in combination with 1 of 4 chemotherapy agents (capecitabine, eribulin, gemcitabine, or vinorelbine) given at the standard doses.
All of the study participants had previously received trastuzumab, all but 1 had previously received pertuzumab, and 91% had previously received ado-trastuzumab emtansine (T-DM1).
Adverse events (AEs) occurring in greater than 20% of patients with margetuximab-cmkb in combination with chemotherapy were fatigue/asthenia (57%), nausea (33%), diarrhea (25%), and vomiting (21%).
Prescribing information includes a boxed warning for left ventricular dysfunction and embryo-fetal toxicity.
Additionally, margetuximab-cmkb may cause infusion related reactions.