BAVENCIO, Avelumab Form

Avelumab (Bavencio®) is a programmed death ligand-1 blocking antibody.
FDA Approved Indication(s) Bavencio is indicated for: • Adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). • Maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. • Patients with locally advanced or metastatic UC who: o Have disease progression during or following platinum-containing chemotherapy. o Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. • First-line treatment, in combination with axitinib, of patients with advanced renal cell carcinoma (RCC). Policy/Criteria Provider must submit documentation (including 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 Bavencio is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Merkel Cell Carcinoma (must meet all):

1. Diagnosis of metastatic or recurrent MCC;

   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 12 years;
   4. Request meets one of the following (a or b): a. Dose does not exceed 800 mg (4 vials) every two 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 8

   CLINICAL POLICY Avelumab B. Urothelial Carcinoma (must meet all):

2. Diagnosis of recurrent, locally advanced, or metastatic UC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member has received platinum-based chemotherapy (e.g., cisplatin, carboplatin);
   5. Prescribed as a single agent;
   6. Request meets one of the following (a or b): a. Dose does not exceed 800 mg (4 vials) every two 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 C. Renal Cell Carcinoma (must meet all):
3. Diagnosis of advanced RCC (e.g., relapse, stage IV disease) with clear cell histology;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed as first-line therapy in combination with Inlyta®; *Prior authorization may be required for Inlyta
   5. Request meets one of the following (a or b): a. Dose does not exceed 800 mg (4 vials) every two 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 D. Other NCCN Recommended Uses (off-label) (must meet all):
4. Diagnosis of one of the following (a, b, or c): a. Gestational trophoblastic neoplasia; b. Endometrial carcinoma; c. Salivary gland tumors;

5. Prescribed or in consultation with an oncologist;

   3. Age ≥ 18 years;
   4. For gestational trophoblastic neoplasia: Prescribed as a single agent following failure of ≥ 2 systemic chemotherapeutic agents (see Appendix B) and member has one of the following (a or b): a. High-risk disease; b. Recurrent or progressive intermediate trophoblastic tumor (placental site trophoblastic tumor or epithelioid trophoblastic tumor) following treatment with a platinum-based regimen; Page 2 of 8

   CLINICAL POLICY Avelumab

6. For endometrial carcinoma, both of the following (a and b): a. Prescribed as a single agent second-line or subsequent treatment (see Appendix B); b. Disease is recurrent or metastatic for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors;
7. For salivary gland tumors, used in combination with Inlyta for recurrent adenoid cystic carcinoma with either of the following (a or b): a. Distant metastases in patients with a performance status of 0-3; b. Unresectable locoregional recurrence or second primary with prior radiation therapy; Prior authorization may be required for Inlyta
8. Request meets one of the following (a or b): a. Dose does not exceed 800 mg (4 vials) every two 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 E. Other diagnoses/indications (must meet 1 or 2):
9. 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
10. 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. All Indications in Section I (must meet all):
11. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Bavencio for a covered indication and has received this medication for at least 30 days;

12. Member is responding positively to therapy; Page 3 of 8

    CLINICAL POLICY Avelumab

13. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 800 mg (4 vials) every two 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):
14. 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

15. 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 dMMR: deficient mismatch repair
    FDA: Food and Drug Administration MCC: Merkel cell carcinoma MSI-H: microsatellite instability-high NCCN: National Comprehensive Cancer Network RCC: renal cell carcinoma UC: urothelial carcinoma Page 4 of 8

    CLINICAL POLICY Avelumab 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 and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies Varies Gestational Trophoblastic Neoplasia Examples of systemic chemotherapeutic agents: bleomycin, carboplatin, cyclophosphamide, dactinomycin, etoposide, gemcitabine, ifosfamide, mesna, methotrexate, paclitaxel, vincristine. Endometrial carcinoma Examples of systemic chemotherapeutic agents: carboplatin/paclitaxel, cisplatin/doxorubicin, carboplatin/paclitaxel/bevacizumab, doxorubicin, topotecan, temsirolimus, ifosfamide 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. Varies Varies Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration
    Indication Dosing Regimen MCC, UC RCC 800 mg IV infusion every 2 weeks until disease progression or unacceptable toxicity 800 mg IV infusion every 2 weeks in combination with axitinib 5 mg PO BID Maximum Dose 800 mg every 2 weeks 800 mg every 2 weeks VI. Product Availability
    Single-dose vials: 200 mg/10 mL (20 mg/mL)
    VII.