ZYKADIA, Ceritinib Form

Ceritinib (Zykadia®) is a tyrosine kinase inhibitor. FDA Approved Indication(s) Zykadia is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA- approved test. 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 Zykadia is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Non-Small Cell Lung Cancer (must meet all):

1. Diagnosis of recurrent, advanced or metastatic NSCLC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Meets one of the following (a or b): a. Disease is ALK positive; b. Disease is ROS1 positive and Zykadia is prescribed as first-line therapy;
2. Prescribed as a single agent;
   6. For Zykadia requests, member must use generic ceritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
3. Request meets one of the following (a or b): a. Dose does not exceed 450 mg (3 tablets) per day; 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 – 12 months or duration of request, whichever is less
   B. Additional NCCN Recommended Uses (off-label) (must meet all):

4. Prescribed for one of the following diagnoses (a - c):
   Page 1 of 6

   CLINICAL POLICY Ceritinib a. Erdheim-Chester disease and (i): i. Disease is symptomatic or relapsed/refractory; b. Inflammatory myofibroblastic tumor (IMT; a soft tissue sarcoma) c. Uterine sarcoma and both (i and ii): i. Presence of IMT; ii. Disease is advanced, recurrent, metastatic, or inoperable;

5. Prescribed by or in consultation with an oncologist or hematologist;
   
   3. Age ≥ 18 years;
   4. Disease is ALK positive;
   5. Prescribed as a single agent;
   6. For Zykadia requests, member must use generic ceritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
6. Request meets one of the following (a or b): a. Dose does not exceed 450 mg (3 tablets) per day; 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 – 12 months or duration of request, whichever is less C. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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):
9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zykadia for a covered indication and has received this medication for at least 30 days;

10. Member is responding positively to therapy; Page 2 of 6

    CLINICAL POLICY Ceritinib

11. For Zykadia requests, member must use generic ceritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
    
    4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 450 mg (3 tablets) per day; 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 – 12 months or duration of request, whichever is less
       B. Other diagnoses/indications (must meet 1 or 2):
12. 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

13. 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 ALK: anaplastic lymphoma kinase FDA: Food and Drug Administration IMT: inflammatory myofibroblastic tumor Appendix B: Therapeutic Alternatives
    Not applicable NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer ROS1: ROS proto-oncogene 1 Page 3 of 6

    CLINICAL POLICY Ceritinib Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration
    Indication ALK-positive NSCLC Dosing Regimen 450 mg PO QD VI. Product Availability
    Tablet: 150 mg Maximum Dose 450 mg/day VII.