Medical Drug Criteria (MDC)

MDC Num:     P1.001.006
MDC Name:   MARGENZA® (margetuximab-cmkb)
MDC ID:        [P1.001.006] [Ac /L / M+ / P+ ] [0.00.00]

Last Review:      September 22, 2025
Next Review:      September 20, 2026

Related MDC: None

MARGENZA® (margetuximab-cmkb)

Summary

Margenza (margetuximab-cmkb) is a HER2/neu receptor antagonist indicated, 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.

Margetuximab-cmkb is a chimeric Fc-engineered IgG1 kappa monoclonal antibody that binds to the extracellular domain of the HER2 protein. Upon binding, it inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain, and mediates antibody-dependent cellular cytotoxicity (ADCC).

OBJECTIVE

To provide a treatment option for adult patients with metastatic HER2-positive breast cancer who have progressed after at least two prior anti-HER2 regimens, ensuring alignment with current FDA-approved indications and NCCN recommendations.

POLICY STATEMENT

Margenza may be considered medically necessary for patients 18 years of age or older with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, if the criteria outlined in the guidelines below are met.

POLICY GUIDELINES

Coverage eligibility for margetuximab-cmkb (Margenza) will be considered when the following criteria are met:
 
Initial approval (12 months) may be granted for treatment of metastatic HER2-positive breast cancer in individuals who have received two or more prior anti-HER2 regimens, including one or more of the following:
 
Pertuzumab + trastuzumab + docetaxel
 
Pertuzumab + trastuzumab + paclitaxel
 
Fam-trastuzumab deruxtecan-nxki
 
Tucatinib + trastuzumab + capecitabine
 
Ado-trastuzumab emtansine

DOSAGE/ADMINISTRATION:

The recommended dose of Margenza is 15 mg/kg, administered as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

REQUIRED MEDICAL INFORMATION

Initial Approval Criteria

a) Diagnosis of metastatic HER2-positive breast cancer; AND

b) Prescribed by an oncologist or hematologist; AND

c) Age ≥ 18 years; AND

d) HER2-positive status confirmed by ONE of the following:

IHC 3+

FISH HER2 gene copy ≥ 6 signals/cell

FISH ratio of HER2 gene/Chr17 ≥ 2.0

e) Member has received ≥ 2 prior anti-HER2 treatments (e.g., trastuzumab, pertuzumab, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan); AND

f) Use is in combination with chemotherapy; AND

g) Not used in combination with another anti-HER2 regimen; AND

h) Dose does not exceed 15 mg/kg every 21 days; AND

i) Documentation of patient’s actual body weight.

Renewal Criteria

Patient is currently receiving margetuximab-cmkb and continues to meet initial approval criteria; AND

Patient demonstrates continued clinical benefit (tumor response or disease stabilization) with an acceptable toxicity profile.

EXCLUSION CRITERIA

None specified.

BENEFIT APPLICATION

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

OTHER CRITERIA

Validate that the treatment regimen is following the most up to date NCCN guidelines recommendations.

Background

Margenza is a novel HER2-directed Fc-engineered monoclonal antibody designed to enhance ADCC compared to trastuzumab. Clinical efficacy is based on the SOPHIA trial, which demonstrated improved progression-free survival in heavily pretreated HER2-positive metastatic breast cancer patients.

REGULATORY STATUS

FDA approval: December 16, 2020.

NCCN Guidelines: Category 2A recommendation for 4th line or later therapy in metastatic HER2-positive breast cancer.

PRACTICE GUIDELINES AND POSITION STATEMENTS

NCCN: Recommends Margenza in combination with chemotherapy as a treatment option in ≥4th line HER2-positive metastatic breast cancer.

REFERENCES

1. Margetuximab-cmkb. In: DRUGDEX [database on the Internet]. Greenwood Village (CO): IBM Corporation; 2023 [cited 2023 September 14]. Available from: www.micromedexsolutions.com. Subscription required to view.
2. MARGENZA(TM) intravenous injection, margetuximab-cmkb intravenous injection. MacroGenics Inc (per manufacturer), Rockville, MD, 2020.
3. FDA approval — Dec 16, 2020.  
4. NDA multidisciplinary review on ADCC and pharmacodynamics.  
5.  SOPHIA trial efficacy and safety publications (Rugo 2021/2023, etc.). 
6. Expanded preclinical profile and pharmacology insights.    
7. Toxicity profile and infusion-related findings.  
8. Critical commentary on positioning vs other regimens.  

Codes

Applicable Modifiers

N/A

Policy History