Tisotumab vedotin-tftv (Tivdak) Form

Tisotumab vedotin-tftv (Tivdak™) is a tissue factor directed antibody and microtubule inhibitor conjugate. FDA Approved Indication(s) Tivdak is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 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 Tivdak is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Cervical Cancer (must meet all):

1. Diagnosis of cervical cancer;
2. Disease is recurrent or metastatic;
3. Prescribed by or in consultation with an oncologist;
4. Age ≥ 18 years;
5. Failure of single-agent or combination chemotherapy regimen (see Appendix B for examples);
   6. Prescribed as single-agent therapy;
6. Documentation of member’s current weight in kilograms;

7. Request meets one of the following (a or b): a. Dose does not exceed 2 mg/kg (up to a maximum dose of 200 mg for members ≥ 100 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: 6 months Page 1 of 7

   CLINICAL POLICY Tisotumab Vedotin-tftv B. Other diagnoses/indications (must meet 1 or 2):

   1. 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
   2. 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. Cervical Cancer (must meet all):
   3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tivdak for a covered indication and has received this medication for at least 30 days;
   4. Member is responding positively to therapy;
8. Prescribed as single-agent therapy;
9. Member is receiving at least 0.9 mg/kg every 3 weeks;
10. Documentation of member’s current weight in kilograms;

11. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 2 mg/kg (up to a maximum dose of 200 mg for patients ≥ 100 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: 12 months
    B. Other diagnoses/indications (must meet 1 or 2):

    1. 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: Page 2 of 7

    CLINICAL POLICY Tisotumab Vedotin-tftv CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

    2. 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. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration 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 paclitaxel/cisplatin ± bevacizumab (Avastin®, Mvasi®, Zirabev™)
       paclitaxel/carboplatin ± bevacizumab (Avastin®, Mvasi®, Zirabev™) topotecan (Hycamtin®) /paclitaxel ± bevacizumab (Avastin®, Mvasi®, Zirabev™) • Paclitaxel: 135 mg/m2 or 175 mg/m2 IV on Day 1 • Cisplatin: 50 mg/m2 IV on Day 1 or 2 • With or without bevacizumab: 15 mg/kg IV on day
       Repeat every 3 weeks until disease progression or unacceptable toxicity • Paclitaxel 135 mg/m2 IV over 3 hours • Carboplatin target AUC 5 IV • With or without bevacizumab: 15 mg/kg IV on day
       Repeat every 3 weeks until disease progression or unacceptable toxicity • Paclitaxel: 175 mg/m2 on day 1 • Topotecan: 0.75 mg/m2 on days 1, 2, and 3
       • With or without bevacizumab: 15 mg/kg IV on day
       Varies Varies paclitaxel/cisplatin Repeat every 3 weeks until disease progression or unacceptable toxicity • Paclitaxel: 135 mg/m2 over 24 hours
       • Cisplatin: 50 mg/m2 on day 1 Varies Page 3 of 7

    CLINICAL POLICY Tisotumab Vedotin-tftv Drug Name Dosing Regimen paclitaxel/carboplatin Repeat every 3 weeks for a maximum of 6 cycles in non-responders or until disease progression or unacceptable toxicity • Paclitaxel 135 mg/m2 IV over 3 hours on day 1 until disease progression or unacceptable toxicity • Carboplatin: Target AUC 5 IV every 3 weeks for 6 to 9 cycles Dose Limit/ Maximum Dose Varies cisplatin/topotecan (Hycamtin®) • Cisplatin: 50 mg/m2 IV on day 1 • Topotecan: 0.75 mg/m2/day IV for days Varies 1, 2, and 3
    paclitaxel/topotecan (Hycamtin®) Keytruda® (pembrolizumab) + paclitaxel/cisplatin ± bevacizumab (Avastin®, Mvasi®, Zirabev™) for PD-L1-positive tumors
    cisplatin carboplatin paclitaxel Repeat every 3 weeks for a maximum of 6 cycles in nonresponders or until disease progression or unacceptable toxicity • Paclitaxel: 175 mg/m2 on day 1 • Topotecan: 0.75 mg/m2 on days 1, 2, and 3
    Repeat every 3 weeks until disease progression or unacceptable toxicity Varies Varies Varies 40 mg/m2 over 4 hours to radiation therapy on days 1, 8, 15, 22, 29, and 36 400 mg/m2 on day 1 every 28 days Varies Varies Varies Varies 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): Ocular toxicity IV. Dosage and Administration
    Indication Cervical cancer Dosing Regimen 2 mg/kg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity Maximum Dose 2 mg/kg, 200 mg for members ≥ 100kg
    Page 4 of 7

    CLINICAL POLICY Tisotumab Vedotin-tftv V. Product Availability
    Intravenous powder for solution, single-dose vial: 40 mg VI.