Pralsetinib (Gavreto) Form

Pralsetinib (Gavreto®) is an oral tyrosine kinase inhibitor of wild-type rearranged during transfection (RET) and oncogenic RET fusions (CCDC6-RET) and mutations (RET V804L, RET V804M, and RET M918T). FDA Approved Indication(s) Gavreto is indicated for the treatment of: • Adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test. • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine- refractory (if radioactive iodine is appropriate).This indication is 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 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 Gavreto 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. Documentation of RET fusion-positive disease (e.g., CCDC6-RET, KIF5B-RET);
   5. Gavreto is not prescribed concurrently with Retevmo™;
   6. Member has not received prior RET targeted therapy (e.g., Retevmo);
   7. Prescribed as a single agent;
   8. For Gavreto requests, member must use pralsetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

2. Request meets one of the following (a, b, or c):* a. Dose does not exceed both of the following (i and ii):
   i. 400 mg per day; Page 1 of 6

   CLINICAL POLICY Pralsetinib ii. 4 capsules per day;
   b. Both of the following (i and ii):
   i. Dose does not exceed both of the following (1 and 2): 1) 800 mg per day;
   2) 8 capsules per day; ii. Prescriber attestation of member’s inability to avoid concomitant use of CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John’s wort); c. 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 – 6 months Commercial – 12 months or duration of request, whichever is less
   B. Thyroid Cancer (must meet all):

3. Diagnosis of one of the following (a or b): a. Differentiated thyroid carcinoma (DTC; oncocytic/Hurthle cell, papillary, follicular); b. Anaplastic thyroid carcinoma (ATC);
4. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 12 years;
   4. Disease is recurrent, advanced or metastatic;
   5. Prescribed as a single agent;
   6. Documentation of RET fusion-positive disease (e.g., CCDC6-RET, KIF5B-RET);
   7. Member is radioactive iodine-refractory (if radioactive iodine is appropriate);
   8. For DTC, disease is not amenable to radioactive iodine therapy;
   9. Gavreto is not prescribed concurrently with Retevmo;
   10. Member has not received prior RET targeted therapy (e.g., Retevmo);
   11. For Gavreto requests, member must use pralsetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

5. Request meets one of the following (a, b, or c): a. Dose does not exceed both of the following (i and ii):
   i. 400 mg per day; ii. 4 capsules per day; b. Both of the following (i and ii):
   i. Dose does not exceed both of the following (1 and 2): 1) 800 mg per day;
   2) 8 capsules per day; ii. Prescriber attestation of member’s inability to avoid concomitant use of CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John’s wort); c. 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 – 6 months Commercial – 12 months or duration of request, whichever is less
   Page 2 of 6

   CLINICAL POLICY Pralsetinib C. Other diagnoses/indications (must meet 1 or 2):

6. 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 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 and CP.PMN.16 for Medicaid; or
7. 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 and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. All Indications in Section I (must meet all):
8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Gavreto for a covered indication and has received this medication for at least 30 days;
9. Member is responding positively to therapy;
   
   3. Gavreto is not prescribed concurrently with Retevmo;
   4. Member has not received prior RET targeted therapy (e.g., Retevmo);
   5. For Gavreto requests, member must use pralsetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
10. If request is for a dose increase, request meets one of the following (a, b, or c): a. New dose does not exceed both of the following (i and ii):
    i. 400 mg per day; ii. 4 capsules per day;
    b. Both of the following (i and ii):
    i. New dose does not exceed both of the following (1 and 2): 1) 800 mg per day;
    2) 8 capsules per day; ii. Prescriber attestation of member’s inability to avoid concomitant use of CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John’s wort);
    c. 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 – 12 months Commercial – 12 months or duration of request, whichever is less
    B. 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): Page 3 of 6

    CLINICAL POLICY Pralsetinib 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 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 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 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 and CP.PMN.53 for Medicaid or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ATC: anaplastic thyroid carcinoma DTC: differentiated thyroid carcinoma FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings None reported
    NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer RET: rearranged during transfection V. Dosage and Administration
    Indication NSCLC, thyroid cancer Dosing Regimen Maximum Dose 400 mg PO QD 800 mg/day with coadministration of strong CYP3A inducers VI. Product Availability
    Capsule: 100 mg VII.