Centene Margenza Coverage & Prior Auth Update

Coverage Criteria

inv-01: Initial Therapy

Covered when ALL of the following are met

Initial Approval - Metastatic HER2-positive breast cancer: 1. Diagnosis of metastatic HER2-positive breast cancer; 2. Prescribed by or in consultation with an oncologist; 3. Age >= 18 years; 4. For metastatic disease: failure of two anti-HER2-based regimens, at least one of which was for metastatic disease, unless contraindicated or intolerant; 5. For recurrent unresectable disease or patients with no response to preoperative systemic therapy: failure of three anti-HER2-based regimens (fourth-line allowance per NCCN 2A) unless contraindicated or intolerant; 6. Prescribed in combination with chemotherapy (e.g., capecitabine, eribulin, gemcitabine, vinorelbine); 7. Dose does not exceed 15 mg/kg every 3 weeks or dose is supported by practice guidelines/peer-reviewed literature for relevant off-label use (prescriber must submit supporting evidence).15 mg/kg every 3 weeks

Prescribed regimen must be FDA-approved or recommended by NCCN.

inv-02: Continuation Therapy

Covered when ALL of the following are met

Continued Therapy: 1. Member is currently receiving Margenza via Centene benefit or has documentation showing the member has received Margenza for at least 30 days; 2. Member is responding positively to therapy; 3. New dose does not exceed 15 mg/kg every 3 weeks; 4. If request is for a dose increase, prescriber must provide justification or supporting evidence for off-label dosing.15 mg/kg every 3 weeks

Approval duration: Medicaid/HIM 12 months; Commercial 6 months or to the member's renewal date, whichever is longer.

inv-03: Coverage criteria (summary of changes)

Policy coverage aligns with FDA label and NCCN recommendations; updated to include specific line-of-therapy indications.

Updated indications: Use in combination with chemotherapy is required per FDA label and NCCN; criteria were added to allow fourth-line use in recurrent unresectable disease and for patients with no response to preoperative systemic therapy to align with NCCN 2A recommendations.

Full clinical criteria located in other sections of the policy not included in this extract

Requests for use of margetuximab-cmkb (Margenza) for non‑FDA approved indications that are not specifically addressed by this clinical policy are not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other evidence of coverage documents.

For Medicaid members, any applicable state Medicaid coverage provisions supersede the terms of this clinical policy when there is a conflict. Providers should consult the relevant state Medicaid manual for specific coverage requirements that apply to margetuximab‑cmkb.

Off‑label requests for margetuximab‑cmkb must meet the plan’s off‑label use requirements. Use for indications that are not FDA‑approved and not addressed in this policy will be considered not authorized unless the prescriber supplies documentation of efficacy and safety consistent with the off‑label use policies referenced above.

Initial Therapy

inv-23: Initial Therapy

Initial coverage criteria

Initial therapy nodes: Diagnosis of metastatic HER2-positive breast cancer; prescribed by or in consultation with an oncologist; age >= 18 years; prior failure of required anti-HER2 regimens as specified (two regimens for metastatic disease; three regimens for recurrent unresectable or no-response preoperative cases to allow fourth-line use per NCCN 2A); prescribed in combination with chemotherapy; dose does not exceed 15 mg/kg every 3 weeks (or an off-label dose supported by guidelines/literature with submitted evidence).15 mg/kg every 3 weeks

Approval duration: Medicaid/HIM 6 months (initial).

inv-24: Initial therapy — requires adherence to FDA label and NCCN recommendations (e.g., combination with chemotherapy).

Initial therapy coverage requires adherence to FDA label and NCCN recommendations (e.g., combination with chemotherapy).

initial therapy: Use must follow the FDA label and NCCN guidance, including administration in combination with chemotherapy. Detailed eligibility criteria are provided in the Initial Approval criteria section.

Continuation / Maintenance Criteria

inv-25: Continuation/Maintenance

Criteria for continued coverage

Continued therapy nodes: Member must have been on therapy at least 30 days or currently receiving Margenza via Centene benefit; member must be responding to therapy; dose must not exceed 15 mg/kg every 3 weeks; dose increases require prescriber justification and supporting evidence for off-label dosing.15 mg/kg every 3 weeks

Approval duration: Medicaid/HIM 12 months; Commercial 6 months or to renewal date.

inv-26: Continued therapy — Template changes applied to continued therapy section; specifics not present in this extract.

Template changes applied to continued therapy section; specifics not present in this extract.

continued therapy updates: Continued therapy section template was updated (2022); no significant substantive changes documented in 2023–2024 reviews. Detailed continued therapy criteria are located elsewhere in the policy.

Step Therapy / Prior Treatment Requirements

Step	Requirement	Supporting details
1	Prior anti-HER2 therapy failure required before approval	For metastatic disease: failure of two anti‑HER2–based regimens, at least one for metastatic disease; for recurrent unresectable disease or patients with no response to preoperative systemic therapy: failure of three anti‑HER2–based regimens (see Appendix B for therapeutic alternatives).

Policy change	Impact on step therapy / line of therapy	Notes
Added fourth-line indication per NCCN 2A (1Q 2025 medical policy update)	Allows use as fourth‑line therapy in select recurrent unresectable disease or patients with no response to preoperative systemic therapy; may alter step‑therapy sequencing by counting prior anti‑HER2 regimens accordingly.	Policy update also reiterates requirement for use in combination with chemotherapy per FDA label; see Initial Approval Criteria for specific regimen and prior‑therapy requirements.

Coding and Dose Information

HCPCS CodesHCPCS

J9353

Injection, margetuximab-cmkb, 5 mg

HCPCS CodesHCPCS

J9353

Injection,margetuximab-cmkb_5 mg

inv-09: Maximum dose — 15 mg/kg every 3 weeks

Maximum dose15 mg/kg every 3 weeks

Dosing contextApplies to initial and continued therapy unless an off-label dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit evidence)

Approval requirementDose increases require prescriber justification or supporting evidence for off‑label use

inv-10: Policy creation date — 01.07.21

Policy creation date01.07.21

Initial P&T approvalP&T Approval Date = 02.21

Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required for Margenza

Prior authorization required for Margetuximab (Margenza). Provider must document diagnosis of metastatic HER2-positive breast cancer, prior anti‑HER2 regimens (see Appendix B) including whether at least one was for metastatic disease (or document contraindication or intolerance), age ≥ 18 years, oncologist involvement (prescribed by or in consultation with an oncologist), planned combination with chemotherapy per FDA label and NCCN recommendations, and dosing not to exceed 15 mg/kg every 3 weeks unless supported by guidelines or peer‑reviewed literature for an off‑label use. Prior authorization may also be required for the accompanying anti‑HER2 regimens.

HCPCS: J9353 (Injection, margetuximab‑cmkb, 5 mg) — billing requires verification of coverage and prior authorization where applicable.
Therapy must be prescribed in combination with chemotherapy (e.g., capecitabine, eribulin, gemcitabine, vinorelbine) per FDA label and NCCN; sequencing/line‑of‑therapy criteria in this policy affect ordering and prior authorization decisions.
Dose limit: generally ≤ 15 mg/kg every 3 weeks; higher/off‑label doses require supporting evidence from guidelines or literature and prescriber documentation.
Prior authorization required documentation: office/chart notes, diagnostic/pathology reports, prior treatment history, labs, and any supporting literature for off‑label dosing or indications.

Background

Margetuximab‑cmkb (Margenza) is an anti‑HER2 monoclonal antibody indicated for adult patients with metastatic HER2‑positive breast cancer in accordance with the FDA‑approved labeling and guideline recommendations. The policy requires adherence to labeled use and referenced guidance; off‑label or non‑policy indications require supporting evidence per off‑label policies. Additionally, for Medicaid members, state Medicaid coverage provisions take precedence where conflicts exist—providers should refer to state Medicaid manuals for relevant directions.

Definitions and Safety Notes

inv-20: HER2 definition — human epidermal growth factor receptor 2

DefinitionHER2 = human epidermal growth factor receptor 2

ContextHER2 status is required to establish eligibility for anti‑HER2 therapy per policy criteria

Abbreviation sourceListed in Appendix A: Abbreviation/Acronym

inv-21: Boxed warnings / contraindications — left ventricular dysfunction and embryo-fetal toxicity

Boxed warningsLeft ventricular dysfunction; embryo‑fetal toxicity

ContraindicationsNone reported in the policy extract

Quantity Limits

inv-29: Margetuximab-cmkb (Margenza) — 15 mg/kg per dose (quantity limits summary)

Quantity limit15 mg/kg per dose

Vial sizeSingle‑dose vial: 250 mg/10 mL

Administration intervalTypically given every 3 weeks per maximum dose guidance

Revision History

2024-12-02annual_review

Added criteria for fourth-line use for recurrent unresectable disease and for patients with no response to preoperative systemic therapy to align with NCCN 2A recommendations; references reviewed and updated.

2025-02-25P&T_approvalLatest

Pharmacy & Therapeutics (P&T) committee approved 1Q 2025 annual review changes adding fourth-line and preoperative nonresponse criteria to align with NCCN 2A.

2022-02-22annual_review