Margetuximab-cmkb (Margenza) Form

Margetuximab-cmkb (Margenza™) is a human epidermal growth factor receptor 2 (HER2)/neu receptor antagonist. FDA Approved Indication(s) Margenza is 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. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Margenza is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Breast Cancer (must meet all):

1. Diagnosis of metastatic HER2-positive breast cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Failure of two anti-HER2-based regimens (see Appendix B), at least one of which was for metastatic disease, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for anti-HER2-based regimens
2. Prescribed in combination with chemotherapy (e.g., capecitabine, eribulin, gemcitabine, vinorelbine);

3. Request meets one of the following (a or b): a. Dose does not exceed 15 mg/kg every 3 weeks; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
   Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer Page 1 of 6

   CLINICAL POLICY Margetuximab-cmkb B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Breast Cancer (must meet all):
6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Margenza for a covered indication and has received this medication for at least 30 days;
7. Member is responding positively to therapy;
   3. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 15 mg/kg every 3 weeks; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
      Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 2 of 6

   CLINICAL POLICY Margetuximab-cmkb

9. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration HER2: human epidermal growth factor receptor 2 Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen Varies Dose Limit/ Maximum Dose Varies Herceptin® (trastuzumab) ± any of the following: • Aromatase inhibitor • Aromatase inhibitor ± Tykerb® (lapatinib) • Fulvestrant (Faslodex®) • Tamoxifen Aromatase inhibitor ± Tykerb (lapatinib) Perjeta® (pertuzumab) + Herceptin (trastuzumab) + either of the following: • Docetaxel • Paclitaxel Kadcyla® (ado-trastuzumab emtansine) Enhertu® (fam-trastruzumab- nxki) Herceptin (trastuzumab) + any of the following: • Paclitaxel ± carboplatin • Docetaxel 3.6 mg/kg IV every 3 weeks (21-day cycle) 5.4 mg/kg IV every 3 weeks 5.4 mg/kg 3.6 mg/kg Varies Varies Page 3 of 6

   CLINICAL POLICY Margetuximab-cmkb Drug Name Dosing Regimen Dose Limit/ Maximum Dose • Vinorelbine
   • Xeloda® (capecitabine) • Tykerb (lapatinib) Tykerb (lapatinib) + Xeloda (capecitabine) Tykerb 1,250 mg PO QD days 1-21 + Xeloda 1,000 mg/m2 PO BID days 1-14 (21-day cycle) Tykerb 1,250 mg/day Xeloda 2,000 mg/m2/day Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): left ventricular dysfunction; embryo-fetal toxicity V. Dosage and Administration
   Indication Breast cancer Dosing Regimen 15 mg/kg IV every 3 weeks Maximum Dose 15 mg/kg VI. Product Availability
   Single-dose vial: 250 mg/10 mL VII.