EPZ-6438 TAZEMETOSTAT EPZ438 Form

Tazemetostat (Tazverik™) is a methyltransferase inhibitor. FDA Approved Indication(s)
Tazverik is indicated for the treatment of:
• Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) not eligible for complete resection. • Adult patients with relapsed or refractory follicular lymphoma (FL) whose tumors are positive for an enhancer of zeste homolog 2 (EZH2) mutation as detected by an FDA- approved test and who have received at least 2 prior systemic therapies.
• Adult patients with relapsed or refractory FL who have no satisfactory alternative treatment options.
__ These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 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 Tazverik is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Epithelioid Sarcoma (must meet all):

1. Diagnosis of ES;

   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 16 years;
   4. For brand Tazverik requests, member must use generic tazemetostat, if available, unless contraindicated or clinically significant adverse effects are experienced;
   5. Disease is metastatic or locally advanced, and not eligible for complete resection;
   6. Tumor demonstrates loss of INI1 gene expression through inactivation, deletion, or mutation of the INI1 (SMARCB-1) gene;
   7. Tazemetostat is prescribed as monotherapy;
   8. Request meets one of the following (a or b):* a. Dose does not exceed 1,600 mg (8 tablets) per day; Page 1 of 7

   CLINICAL POLICY Tazemetostat 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. Follicular Lymphoma (must meet all):

2. Diagnosis of FL;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. For brand Tazverik requests, member must use generic tazemetostat, if available, unless contraindicated or clinically significant adverse effects are experienced;
3. One of the following (a or b): a. If tumor is positive for EZH2 mutation: member has relapsed/refractory disease after ≥ 2 prior therapies (see Appendix B for examples);Prior authorization may be required. b. If EZH2 mutation status is negative or unknown, one of the following (i or ii): i. Failure of Aliqopa™, unless clinically significant adverse effects are experienced or all are contraindicated;Prior authorization may be required. ii. Member has relapsed/refractory disease and no satisfactory alternative treatment options;
4. Member does not have a history of or current CNS metastases;
   7. Request meets one of the following (a or b): a. Dose does not exceed 1,600 mg (8 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):
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 Page 2 of 7

   CLINICAL POLICY Tazemetostat 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):

7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tazverik for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   3. For brand Tazverik requests, member must use generic tazemetostat, 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 or b): a. New dose does not exceed 1,600 mg (8 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):
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:
    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. Page 3 of 7

    Dose Limit/ Maximum Dose Varies CLINICAL POLICY Tazemetostat IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ES: epithelioid sarcoma EZH2: enhancer of zeste homolog 2 FDA: Food and Drug Administration FL: follicular lymphoma
    NCCN: National Comprehensive Cancer Network STS: soft tissue sarcoma 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 Follicular Lymphoma Examples of first-line, second-line and subsequent therapies: • bendamustine + Gazyva® or Varies rituximab • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) + Gazyva® or rituximab • CVP (cyclophosphamide, vincristine, prednisone) + Gazyva® or rituximab • Revlimid® + rituximab • Revlimid® + Gazyva® • Single-agent examples: rituximab; Gazyva®; Revlimid® Aliqopa® (copanlisib) FL (third-line and subsequent therapy): 60 mg IV on days 1, 8, and 15 of a 28-day treatment cycle 60 mg/dose/ week 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. Appendix C: Contraindications/Boxed Warnings Not reported V. Dosage and Administration
    Indication ES, FL Dosing Regimen 800 mg PO BID until disease progression or unacceptable toxicity Maximum Dose 1,600 mg/day VI. Product Availability
    Tablet: 200 mg Page 4 of 7

    CLINICAL POLICY Tazemetostat VII.