BRAFTOVI, Encorafenib Form

Encorafenib (Braftovi®) is a kinase inhibitor.
FDA Approved Indication(s) Braftovi is indicated: • In combination with binimetinib (Mektovi®), 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 cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. In combination with binimetinib (Mektovi®), 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. • • Limitation(s) of use: Braftovi is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC.
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 Braftovi 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 Mektovi, unless Braftovi/Mektovi combination therapy is contraindicated;
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   CLINICAL POLICY Encorafenib

3. For adjuvant therapy or limited resectable melanoma: Both of the following (a and b):
   a. Prescribed in combination with Mektovi; 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 Braftovi requests, member must use generic encorafenib, 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 both of the following (i and ii):
   i. 450 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
   B. Colon Cancer, Rectal Cancer, Appendiceal Adenocarcinoma (must meet all):
5. Diagnosis of colon cancer, rectal cancer, or appendiceal adenocarcinoma with BRAF V600E mutation;
6. Disease is unresectable, advanced, or metastatic;
   3. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. Prescribed in combination with either Erbitux® or Vectibix®;
   6. One of the following (a or b): a. Member previously received adjuvant therapy (e.g., FOLFOX, CapeOX) within the past 12 months; b. Request is for subsequent therapy following previous treatment (e.g., oxaliplatin- or irinotecan-based therapy, Opdivo®, Keytruda®, FOLFOX, CapeOX);
7. For Braftovi requests, member must use generic encorafenib, 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. 300 mg per day; ii. 4 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. Non-Small Cell Lung Cancer (must meet all):

9. 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; Page 2 of 8

   CLINICAL POLICY Encorafenib

10. Prescribed in combination with Mektovi;
    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
11. Member has not received prior BRAF-targeted therapy (e.g., Tafinlar®, Tafinlar® (see Appendix B); with Mekinist®);
12. For Braftovi requests, member must use generic encorafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
13. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii): i. 450 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 D. Other diagnoses/indications (must meet 1 or 2):
14. 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
15. 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):
16. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Braftovi for a covered indication and has received this medication for at least 30 days;

17. Member is responding positively to therapy;

    3. For Braftovi requests, member must use generic encorafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
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    CLINICAL POLICY Encorafenib

18. If request is for a dose increase, request meets one of the following (a, b, c, or d): a. Melanoma: New dose does not exceed both of the following (i and ii):
    i. 450 mg per day; ii. 6 capsules per day;
    b. Colon or rectal cancer: New dose does not exceed both of the following (i and ii):
    i. 300 mg per day; ii. 4 capsules per day; c. Non-small cell lung cancer: New dose does not exceed both of the following (i and ii): i. 450 mg per day;
    ii. 6 capsules per day; d. 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):
19. 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

20. 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 Page 4 of 8

    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 Colorectal Cancer FOLFOX (fluorouracil, leucovorin, and oxaliplatin); CapeOX (capecitabine and oxaliplatin); FOLFIRI (irinotecan, leucovorin, 5-FU); FOLFOXIRI (irinotecan, oxaliplatin, leucovorin, fluorouracil); IROX (oxaliplatin, irinotecan); oxaliplatin and irinotecan Opdivo (nivolumab) Keytruda (pembrolizumab) Melanoma Tafinlar® and Mekinist® Varies Varies Monotherapy: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks With ipilimumab: 3 mg/kg IV, followed by ipilimumab 1 mg/kg on the same day every 3 weeks for 4 doses, then nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks 200 mg IV every 3 weeks OR 400 mg every 6 weeks up to 24 months Tafinlar 150 mg PO BID with Mekinist 2 mg PO QD Monotherapy: 480 mg/dose With ipilimumab: 3 mg/kg/dose 200 mg every 3 weeks OR 400 mg every 6 weeks Tafinlar: 300 mg/day Mekinist: 2 mg/day Varies Varies Non-Small Cell Lung Cancer Platinum-based chemotherapy (carboplatin, cisplatin) Anti-PD-1 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 Varies Varies Page 5 of 8

    CLINICAL POLICY Encorafenib Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration
    Indication Melanoma Colon cancer, rectal cancer Non-small cell lung cancer Dosing Regimen 450 mg PO QD in combination with Mektovi until disease progression or unacceptable toxicity 300 mg PO QD with either Erbitux (labeled) or Vectibix (off-label) 450 mg PO QD in combination with Mektovi until disease progression or unacceptable toxicity Maximum Dose 450 mg/day 300 mg/day 450 mg/day VI. Product Availability
    Capsule: 75 mg VII.