MEKTOVI, Binimetinib Form

Binimetinib (Mektovi®) is a kinase inhibitor.
FDA Approved Indication(s) Mektovi is indicated: • In combination with encorafenib (Braftovi®), for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA- approved test. In combination with encorafenib (Braftovi®), for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, 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 Mektovi is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Melanoma (must meet all):

1. Diagnosis of melanoma with BRAF V600E or V600K mutation;
   2. Disease is for treatment of one of the following (a, b, or c): a. Unresectable or metastatic melanoma; b. Stage III melanoma as adjuvant therapy; c. Limited resectable melanoma;
2. Prescribed by or in consultation with an oncologist;
   
   4. Age ≥ 18 years;
   5. For unresectable or metastatic melanoma: Prescribed in combination with Braftovi™; unless Braftovi/Mektovi combination is contraindicated;

3. For adjuvant therapy or limited resectable melanoma: Both of the following (a and b):
   a. Prescribed in combination with Braftovi; b. Member has unacceptable toxicities to Tafinlar®/Mekinist®, or Tafinlar/Mekinist are not appropriate for the member on the basis of agent side-effect profiles;

   7. For Mektovi requests, member must use generic binimetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
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   CLINICAL POLICY Binimetinib

4. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii): i. 90 mg per day; ii. 6 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. Non-Small Cell Lung Cancer (must meet all):
5. Diagnosis of advanced, metastatic, or recurrent NSCLC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is positive for a BRAF V600 E mutation;
   5. Prescribed in combination with Braftovi;
   6. One of the following (a or b): a. Member is treatment-naïve; b. Request is for subsequent therapy following progression on prior systemic therapy
6. Member has not received prior BRAF-targeted therapy (e.g., Tafinlar®, Tafinlar® (see Appendix B); with Mekinist®);
7. For Mektovi requests, member must use generic binimetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
8. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii): i. 90 mg per day;
   ii. 6 capsules 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. Histiocytic Neoplasms (off-label) (must meet all):
   
   1. Diagnosis of Langerhans cell histiocytosis;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Disease meets one of the following (a, b, or c): a. Positive for mitogen-activated protein (MAP) kinase pathway mutation,
      b. No detectable mutation; c. Mutation testing not available;

9. Prescribed as a single agent;

   6. For Mektovi requests, member must use generic binimetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
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   CLINICAL POLICY Binimetinib

10. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
    i. 90 mg per day; ii. 6 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
    D. Other diagnoses/indications (must meet 1 or 2):
11. 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
12. 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):
13. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Mektovi for a covered indication and has received this medication for at least 30 days;

14. Member is responding positively to therapy;

    3. For Mektovi requests, member must use generic binimetinib, 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 both of the following (i and ii)
       i. 90 mg per day; ii. 6 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
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    CLINICAL POLICY Binimetinib B. Other diagnoses/indications (must meet 1 or 2):

15. 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

16. 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 BRAF: B-Raf proto-oncogene, serine/threonine kinase
    FDA: Food and Drug Administration NSCLC: non-small cell lung cancer 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 Melanoma Tafinlar® and Mekinist® Tafinlar 150 mg PO BID with Mekinist 2 mg PO QD Tafinlar: 300 mg/day Mekinist: 2 mg/day Non-Small Cell Lung Cancer Platinum-based chemotherapy (carboplatin, cisplatin) Anti-PD-1 Varies Varies Varies Varies Page 4 of 7

    CLINICAL POLICY Binimetinib Drug Name Dosing Regimen Dose Limit/ Maximum Dose Keytruda® (pembrolizumab) Opdivo® (nivolumab) Libtayo® (cemiplimab- rwlc) Anti-PD-L1 Tecentriq® (atezolizumab) Imfinzi® (durvalumab) 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 Melanoma Non-small cell lung cancer Dosing Regimen 45 mg PO BID, approximately 12 hours apart, in combination with Braftovi until disease progression or unacceptable toxicity 45 mg PO BID, approximately 12 hours apart, in combination with Braftovi until disease progression or unacceptable toxicity Maximum Dose 90 mg/day 90 mg/day VI. Product Availability
    Tablet: 15 mg VII.