TASIGNA, Nilotinib HCl Form

Nilotinib (Tasigna®) is a kinase inhibitor. FDA Approved Indication(s) Tasigna is indicated for the treatment of:
• Adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML- CP).* • Adult patients with Ph+ CML-CP and accelerated phase (Ph+ CML-AP) CML resistant or intolerant to prior therapy that included imatinib. • Pediatric patients greater than or equal to 1 year of age with Ph+ CML-CP and CML-AP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy. 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 Tasigna is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Myeloid Leukemia (must meet all):

1. Diagnosis of Ph+ (BCR-ABL1-positive) CML;
   
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Member does not have the following mutations: T315I, Y253H, E255K/V, F359V/C/I;
2. One of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib; b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);
3. For brand Tasigna requests, member must use generic nilotinib, 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 800 mg 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
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   CLINICAL POLICY Nilotinib Approval duration:
   Medicaid/HIM - 6 months Commercial - 12 months or duration of request, whichever is less B. Acute Lymphoblastic Leukemia (off-label) (must meet all):

5. Diagnosis of Ph+ (BCR-ABL1-positive) acute lymphoblastic leukemia (ALL);
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Member does not have the following mutations: T315I, Y253H, E255K/V, F359V/C/I , G250E;
6. One of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib; b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);
7. For brand Tasigna requests, member must use generic nilotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
8. Dose is within FDA maximum limit for any FDA-approved indication or 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. Gastrointestinal Stromal Tumor (off-label) (must meet all):
9. Diagnosis of gastrointestinal stromal tumor (GIST, a soft tissue sarcoma);
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Failure of imatinib, Quinlock™, Sutent®, Sprycel ®, or Stivarga® unless contraindicated or clinically significant adverse effects are experienced;
      *Prior authorization may be required.
10. For brand Tasigna requests, member must use generic nilotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
11. Dose is within FDA maximum limit for any FDA-approved indication or 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. Myeloid/Lymphoid Neoplasms (off-label) (must meet all):
12. Diagnosis of lymphoid, myeloid or mixed lineage neoplasms with eosinophilia and ABL1 rearrangement in blast or chronic phase;

13. Prescribed by or in consultation with an oncologist or hematologist;

    3. Age ≥ 18 years;
    4. One of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib; Page 2 of 9

    CLINICAL POLICY Nilotinib b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);

14. For brand Tasigna requests, member must use generic nilotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
15. Dose is within FDA maximum limit for any FDA-approved indication or 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 E. Off-Label Indications (must meet all):
16. Diagnosis of one of the following (a or b): a. Pigmented villonodular synovitis/tenosynovial giant cell tumor; b. KIT-positive metastatic or unresectable melanoma as second-line or subsequent therapy (i.e., following BRAF-targeted therapy);
17. Prescribed by or in consultation with an oncologist or hematologist;
    
    3. Age ≥ 18 years;
    4. One of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib; b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);
18. For brand Sprycel requests, member must use generic dasatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
19. Dose is within FDA maximum limit for any FDA-approved indication or 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
    F. Other diagnoses/indications (must meet 1 or 2):
20. 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

21. 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 Page 3 of 9

    CLINICAL POLICY Nilotinib 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):

22. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tasigna for a covered indication and has received this medication for at least 30 days;
23. Member is responding positively to therapy;
    3. For brand Tasigna requests, member must use generic nilotinib, 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 800 mg 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):
24. 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

25. 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.
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    CLINICAL POLICY Nilotinib IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALL: acute lymphoblastic leukemia CML: chronic myeloid leukemia FDA: Food and Drug Administration GIST: gastrointestinal stromal tumor
    Ph+: positive Philadelphia chromosome 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. Dose Limit/ Maximum Dose 800 mg/day
    Drug Name Dosing Regimen imatinib (Gleevec)
    ALL: • Adult: 600 mg/day PO for relapsed / refractory Ph+ ALL • Pediatric: 340 mg/m2/day PO in combination with chemotherapy for newly diagnosed Ph+ ALL
    CML: • Adult: o 400-600 mg/day PO for chronic phase o 600-800 mg/day PO for accelerated phase or blast crisis (800 mg given as 400 BID) • Pediatric: 340 mg/m2/day PO for chronic phase
    GIST: 400 mg PO QD to 800 PO BID
    MLNE: 100-400 mg PO QD [NCCN] GIST: 50 mg PO QD
    Sutent (sunitinib) Stivarga (regorafenib) GIST: 160 mg PO QD for the first 21 days 50 mg/day 160 mg/day Quinlock (ripretinib) Sprycel (dasatinib) 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. 150 mg/day 140 mg/day of each 28-day cycle GIST: 150 mg PO QD GIST: 70 mg PO BID Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypokalemia, hypomagnesemia, long QT syndrome
    • Boxed warning(s): QT prolongation, sudden death
    Appendix D: States with Regulations against Redirections in Certain Oncology Settings State Step Therapy Prohibited? Yes FL Notes For stage 4 metastatic cancer and associated conditions. Page 5 of 9

    CLINICAL POLICY Nilotinib State Step Therapy Prohibited? Yes GA IA LA NV OH PA TN TX Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat
    the cancer or any symptom thereof of the covered person Applies to HIM requests only For stage 4 metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions V. Dosage and Administration
    Indication Newly diagnosed Ph+ CML- CP Resistant/intolerant Ph+ CML-CP or Ph+ CML-AP Dosing Regimen Adults: 300 mg PO BID Pediatrics: 230 mg/m2 PO BID, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg) Adults: 400 mg PO BID Pediatrics: 230 mg/m2 PO BID, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg) Maximum Dose Adults: 600 mg/day Pediatrics: 800 mg/day Adults and pediatrics: 800 mg/day VI. Product Availability
    Capsules: 50 mg, 150 mg, 200 mg VII.