MacroGenics Announces FDA Approval of MARGENZA? for Patients with Pretreated Metastatic HER2-Positive Breast Cancer
- MARGENZA (margetuximab-cmkb) is the first HER2-targeted therapy to have improved progression-free survival (PFS) versus Herceptin? (trastuzumab), both combined with chemotherapy,?in a head-to-head Phase 3 clinical trial
- MARGENZA is approved, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease
- Product launch anticipated in March of 2021
- Conference call scheduled for?Thursday, December 17,?2020 at?8:00 a.m. ET
- Left Ventricular Dysfunction:?MARGENZA may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate cardiac function prior to and during treatment. Discontinue MARGENZA treatment for a confirmed clinically significant decrease in left ventricular function.
- Embryo-Fetal Toxicity:?Exposure to MARGENZA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.
- Left ventricular cardiac dysfunction can occur with MARGENZA.
- MARGENZA has not been studied in patients with a pretreatment LVEF value of <50%, a prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV.
- Withhold MARGENZA for =16% absolute decrease in LVEF from pre-treatment values or LVEF below institutional limits of normal (or 50% if no limits available) and =10% absolute decrease in LVEF from pretreatment values.
- Permanently discontinue MARGENZA if LVEF decline persists greater than 8 weeks, or dosing is interrupted more than 3 times due to LVEF decline.
- Evaluate cardiac function within 4 weeks prior to and every 3 months during and upon completion of treatment. Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan.
- Monitor cardiac function every 4 weeks if MARGENZA is withheld for significant left ventricular cardiac dysfunction.
- Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman. Post-marketing studies of other HER-2 directed antibodies during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
- Verify pregnancy status of women of reproductive potential prior to initiation of MARGENZA.
- Advise pregnant women and women of reproductive potential that exposure to MARGENZA during pregnancy or within 4 months prior to conception can result in fetal harm.
- Advise women of reproductive potential to use effective contraception during treatment and for 4 months following the last dose of MARGENZA.
- MARGENZA can cause IRRs. Symptoms may include fever, chills, arthralgia, cough, dizziness, fatigue, nausea, vomiting, headache, diaphoresis, tachycardia, hypotension, pruritus, rash, urticaria, and dyspnea.
- Monitor patients during and after MARGENZA infusion. Have medications and emergency equipment to treat IRRs available for immediate use.
- In patients experiencing mild or moderate IRRs, decrease rate of infusion and consider premedications, including antihistamines, corticosteroids, and antipyretics. Monitor patients until symptoms completely resolve.
- Interrupt MARGENZA infusion in patients experiencing dyspnea or clinically significant hypotension and intervene with supportive medical therapy as needed. Permanently discontinue MARGENZA in all patients with severe or life-threatening IRRs.