Ripretinib (Qinlock) Form

Ripretinib (Qinlock™) is a kinase inhibitor. FDA Approved Indication(s) Qinlock is indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. 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 Qinlock is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Gastrointestinal Stromal Tumor (must meet all):

1. Diagnosis of unresectable, locally advanced, recurrent, progressive, or metastatic GIST;
2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Request meets one of the following (a or b): a. Failure of all of the following, unless clinically significant adverse effects are experienced or all are contraindicated: imatinib, Sutent® or Sprycel®, and Stivarga®;Prior authorization is required for imatinib, Sutent, and Stivarga. i. b. For members with PDGFRA exon 18 mutation, one of the following (i or ii): If D842V mutation positive, failure of Ayvakit™ and Sprycel®, unless clinically significant adverse effects are experienced or both are contraindicated; ii. If positive for mutation other than D842V, failure of Ayvakit, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization is required for Ayvakit and Sprycel
3. Member does not have active central nervous system metastases;
   6. For Qinlock requests, member must use ripretinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

4. Request meets one of the following (a or b):* a. Dose does not exceed 150 mg (3 tablets) per day; Page 1 of 6

   CLINICAL POLICY Ripretinib 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 Legacy WellCare – 12 months
   Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

5. 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
6. 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. Gastrointestinal Stromal Tumor (must meet all):
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Qinlock for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   3. For Qinlock requests, member must use ripretinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

9. If request is for a dose increase, request meets one of the following (a, b, or c): a. New dose does not exceed 150 mg (3 tablets) per day; b. New dose does not exceed 300 mg (6 tablets) per day and member experienced disease progression with 150 mg per day dosing;
   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/Legacy WellCare – 12 months Commercial – 12 months or duration of request, whichever is less Page 2 of 6

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

10. 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

11. 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:
    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
    GIST: gastrointestinal stromal tumor PDGFRA: platelet derived growth factor receptor α 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 imatinib (Gleevec®) Sutent® (sunitinib) Stivarga® (regorafenib) Ayvakit® (avapritinib) GIST PDGFRA exon 18 mutation: 300 mg GIST: 400 mg PO QD
    GIST: 50 mg PO QD 4 weeks on/2 weeks off GIST: 160 mg PO QD 21 days on/7 days off Sprycel® (dasatinib) PO QD GIST PDGFRA exon 18 D842V mutation: 70 mg PO BID Dose Limit/ Maximum Dose 800 mg/day 87.5 mg/day 160 mg/day 300 mg/day 140 mg/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. Page 3 of 6

    CLINICAL POLICY Ripretinib Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration
    Indication GIST Dosing Regimen 150 mg PO QD
    VI. Product Availability
    Tablet: 50 mg Maximum Dose 150 mg/day (300 mg/day if disease progression with 150 mg per day dosing)
    VII.