MARGENZA (margetuximab-cmkb) delivered more time without disease progression¹

MARGENZA delivered a 24% reduction in risk of disease progression or death¹

*PFS was evaluated by blinded independent central review (BICR).
^aBased on stratified Cox Model.
^b+ censored indicates censored data.

Explore the SOPHIA Study, including Study Design, the complete list of Premedications, and Safety Profile seen in the study.

Additional efficacy endpoints

^cHR=0.95 (95% CI, 0.77-1.17). The OS analysis for the intent-to-treat population did not demonstrate a statistically significant advantage.
^dAssessed per BICR.
^eBased on Kaplan-Meier estimates.

Explore prespecified exploratory subgroups by Fc𝛄 receptor genotype

See Exploratory PFS Analysis by CD16A Genotype

See Exploratory OS Analysis by CD16A Genotype

SOPHIA study design

The efficacy and safety of MARGENZA plus chemotherapy compared with trastuzumab plus chemotherapy was evaluated in SOPHIA, a randomized, multicenter, open-label trial of 536 metastatic HER2-positive breast cancer patients^† who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

^†IHC 3+ or ISH-amplified HER2‑positive.

^fThe median number of prior lines of therapy in the locally advanced/metastatic setting was 2 (range: 1-4). All study patients had previously received trastuzumab, all but 1 patient had previously received pertuzumab, and 91% had previously received ado-trastuzumab emtansine; 47% had visceral disease, 57% had bone metastases, 13% had brain metastases, and 60% were hormone receptor positive.

• The main efficacy outcome measures were PFS by BICR and OS. Additional efficacy outcome measures were ORR and DOR assessed by BICR
• Patients were randomized (1:1) to MARGENZA plus chemotherapy or trastuzumab plus chemotherapy. Randomization was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), number of lines of therapy in the metastatic setting (≤2, >2), and number of metastatic sites (≤2, >2)
• Patients were required to have progressed on or after the most recent line of therapy. Prior radiotherapy and hormonal therapy were allowed
• Patients were treated with MARGENZA or trastuzumab in combination with chemotherapy until disease progression or unacceptable toxicity
• Patients received MARGENZA intravenously at a dose of 15 mg/kg every 3 weeks administered over 120 minutes for the initial administration and then over 30 to 120 minutes thereafter

Premedications in the SOPHIA Study

Premedications and prophylaxis for chemotherapy³

• In the SOPHIA trial, standard premedications for the administration of the cytotoxic chemotherapy were employed. For chemotherapy, recommendations made in the locally approved label should be followed for each agent
• When MARGENZA infusions coincided on the same day with cytotoxic chemotherapy administration, the same premedications for the chemotherapy were employed
• The following premedications were made available as per the SOPHIA study protocol and were given to a patient within 30 minutes prior to administering MARGENZA on those days upon which that administration was not preceded by a chemotherapeutic agent or if no premedication was employed for that chemotherapy
• Acetaminophen 650 mg-1000 mg orally (PO) or ibuprofen 400 mg PO
• Diphenhydramine 50 mg PO or IV or equivalent H1 antagonist
• Ranitidine^‡ 300 mg PO or IV or equivalent H2 antagonist
• Dexamethasone 10 mg IV or equivalent (for patients at high risk)

^‡Effective April 1, 2020, the FDA requested manufacturers to withdraw all prescription and over-the-counter ranitidine drugs from market.

See dosage and administration information

MARGENZA has a well-characterized safety profile

Safety of MARGENZA in combination with chemotherapy¹

^gIncludes headache and migraine.
^hIncludes abdominal pain, abdominal discomfort, lower abdominal pain, and upper abdominal pain.
ⁱIncludes peripheral neuropathy, peripheral sensory neuropathy, peripheral motor neuropathy, and neuropathy.

Serious adverse reactions occurred in 16% of patients who received MARGENZA

• Serious adverse reactions in >1% of patients included febrile neutropenia (1.5%), neutropenia/neutrophil count decrease (1.5%), and infusion-related reactions (1.1%)
• Fatal adverse reactions occurred in 1.1% of patients who received MARGENZA, including viral pneumonia (0.8%) and aspiration pneumonia (0.4%)

Permanent discontinuation due to an adverse reaction occurred in 3% of patients who received MARGENZA

• Adverse reactions that resulted in permanent discontinuation in >1% of patients who received MARGENZA included left ventricular dysfunction and infusion-related reactions
• Dosage interruptions due to an adverse reaction occurred in 11% of patients who received MARGENZA. Adverse reactions that required dosage interruption in >5% of patients who received MARGENZA included infusion-related reactions

H1 antagonist=histamine H1 receptor antagonist; H2 antagonist=histamine H2 receptor antagonist; IHC=immunohistochemistry; ISH=in situ hybridization; IV=intravenous; OS=overall survival; PFS=progression-free survival.

References:

1. MARGENZA Prescribing Information. MacroGenics, Inc.

2. Rugo HS, Im S, Cardoso F, et al. Phase 3 SOPHIA study of margetuximab + chemotherapy versus trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: Final overall survival analysis. Presented at San Antonio Breast Cancer Symposium on December 9, 2021 (#2484).

3. Data on File. Clinical Trial Protocol: CP MGAH22 04. Protocol Amendment 3.