Enfortumab Vedotin-ejfv (Padcev) Form

Enfortumab vedotin-ejfv (Padcev®) is a Nectin-4-directed antibody and microtubule inhibitor conjugate. FDA Approved Indication(s) Padcev is indicated:
• In combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer • As a single agent for the treatment of adult patients with locally advanced or metastatic urothelial cancer who:
o have previously received a programmed death receptor-1 (PD-1) or programmed death- ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy, or o are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy 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 Padcev is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Urothelial Carcinoma (must meet all):

1. Diagnosis of recurrent, locally advanced, or metastatic (stage IV) urothelial carcinoma;

2. Prescribed by or in consultation with an oncologist or urologist;

   3. Age ≥ 18 years;
   4. One of the following (a or b): a. Prescribed as a single agent, and one of the following (i or ii): i. Failure of both of the following (1 and 2): 1) Platinum-containing chemotherapy (see Appendix B); 2) PD-1 or PD-L1 inhibitor (see Appendix B); ii. Member is ineligible for cisplatin-containing chemotherapy and has previously received one or more prior lines of therapy (see Appendix B); b. Prescribed in combination with Keytruda®;
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   CLINICAL POLICY Enfortumab Vedotin-ejfv

3. Request meets one of the following (a, b, or c): a. If prescribed as a single agent: Dose does not exceed 1.25 mg/kg (up to 125 mg) on days 1, 8, and 15 of a 28-day cycle; b. If prescribed in combination with Keytruda: Dose does not exceed 1.25 mg/kg (up to 125 mg) on days 1 and 8 of a 21-day cycle; c. 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
   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.190 for commercial, HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Urothelial Carcinoma (must meet all):
6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Padcev for a covered indication and has received this medication for at least 28 days;

7. Member is responding positively to therapy;

   3. If request is for a dose increase, request meets one of the following (a, b, or c): a. If prescribed as a single agent: New dose does not exceed 1.25 mg/kg (up to 125 mg) on days 1, 8 and 15 of a 28-day cycle; b. If prescribed in combination with Keytruda: New dose does not exceed 1.25 mg/kg (up to 125 mg) on days 1 and 8 of a 21-day cycle; c. 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 Page 2 of 7

   CLINICAL POLICY Enfortumab Vedotin-ejfv 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

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.190 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.190 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 PD-1: programmed death receptor-1 PD-L1: programmed death-ligand NCCN: National Comprehensive Cancer Network 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 Dose Limit/ Maximum Dose Varies
   Examples of platinum-containing regimens DDMVAC (dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin)
   gemcitabine with either cisplatin or carboplatin
   Examples of PD-1 inhibitors Keytruda® (pembrolizumab) Varies
   Varies
   Varies
   Varies
   Varies
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   CLINICAL POLICY Enfortumab Vedotin-ejfv Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies
   Varies
   Varies
   Varies
   10 mg/kg IV infusion every 2 weeks Varies 800 mg IV infusion once every 2 weeks Varies Opdivo® (nivolumab) Examples of PD-L1 inhibitors Tecentriq® (atezolizumab) Imfinzi® (durvalumab) Bavencio® (avelumab) Other recommended regimens gemcitabine gemcitabine and paclitaxel ifosfamide, doxorubicin, gemcitabine 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
   Varies
   Varies
   Varies
   Varies
   Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): serious skin reactions
   V. Dosage and Administration
   Indication Dosing Regimen Urothelial cancer As a single agent: 1.25 mg/kg (up to a maximum dose of 125 mg) given as an IV infusion over 30 minutes on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity Maximum Dose See dosing regimen In combination with Keytruda: 1.25 mg/kg (up to a maximum dose of 125 mg) given as an IV infusion over 30 minutes on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity VI. Product Availability
   Single-dose vial for injection: 20 mg, 30 mg VII.