Selpercatinib (Retevmo) Form

Selpercatinib (Retevmo®) is a kinase inhibitor. FDA Approved Indication(s)
Retevmo is indicated for the treatment of: • Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test
• Adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy • Adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer with RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) • Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options _ 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 Retevmo 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., KIF5B-RET);
   5. Retevmo is not prescribed concurrently with Gavreto™;
   6. Member has not received prior RET targeted therapy (e.g., Gavreto);
   7. Prescribed as a single agent; Page 1 of 8

   CLINICAL POLICY Selpercatinib

2. For brand Retevmo requests, member must use generic selpercatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
3. Request meets one of the following (a, b, or c): a. Weight < 50 kg: Dose does not exceed both (i and ii): i. 240 mg per day; ii. 4 capsules per day; b. Weight ≥ 50 kg: Dose does not exceed both (i and ii): i. 320 mg per day; ii. 4 capsules per day; 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/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
   B. Thyroid Cancer (must meet all):
4. Diagnosis of one of the following (a, b, or c): a. MTC; b. Differentiated thyroid carcinoma (DTC; Hurthle cell, papillary, follicular); c. Anaplastic thyroid carcinoma (ATC);
5. Prescribed by or in consultation with an oncologist;
   
   3. Age ≥ 12 years;
   4. Disease is recurrent, advanced, or metastatic;
   5. For MTC, documentation of RET mutant-positive disease (e.g., RET M918T);
   6. For DTC or ATC, both of the following (a and b): a. Documentation of RET fusion-positive disease (e.g., CCDC6-RET, KIF5B-RET); b. Member is radioactive iodine-refractory (if radioactive iodine is appropriate);
6. Retevmo is not prescribed concurrently with Gavreto;
   8. Member has not received prior RET targeted therapy (e.g., Gavreto);
   9. Prescribed as a single agent;
   10. For brand Retevmo requests, member must use generic selpercatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

7. Request meets one of the following (a, b, or c): a. Weight < 50 kg: Dose does not exceed both (i and ii): i. 240 mg per day; ii. 4 capsules per day; b. Weight ≥ 50 kg: Dose does not exceed both (i and ii): i. 320 mg per day; ii. 4 capsules per day; 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/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
   Page 2 of 8

   CLINICAL POLICY Selpercatinib C. RET Fusion-Positive Solid Tumors (must meet all):

8. Diagnosis of a locally advanced or metastatic solid tumor (see Appendix D for examples);
9. Prescribed by or in consultation with an oncologist;
   3. Documentation of RET fusion-positive disease;
   4. One of the following (a or b): a. Disease has progressed on or following prior systemic treatment; b. Member has no satisfactory alternative treatment options;
10. Retevmo is not prescribed concurrently with Gavreto;
    6. Member has not received prior RET targeted therapy (e.g., Gavreto);
    7. Prescribed as a single agent;
    8. For brand Retevmo requests, member must use generic selpercatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
11. Request meets one of the following (a, b, or c): a. Weight < 50 kg: Dose does not exceed both (i and ii): i. 240 mg per day; ii. 4 capsules per day; b. Weight ≥ 50 kg: Dose does not exceed both (i and ii): i. 320 mg per day; ii. 4 capsules per day; 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/HIM – 6 months Commercial – 12 months or duration of request, whichever is less D. Histiocytic Neoplasms (off-label) (must meet all):
12. Diagnosis of one of the following histiocytic neoplasms (a, b, or c): a. Erdheim-Chester Disease
    b. Langerhans Cell Histiocytosis; c. Rosai-Dorfman Disease;
13. Prescribed by or in consultation with an oncologist or hematologist;
    3. Documentation of RET fusion-positive disease;
    4. Retevmo is not prescribed concurrently with Gavreto;
    5. Member has not received prior RET targeted therapy (e.g., Gavreto);
    6. Prescribed as a single agent;
    7. For brand Retevmo requests, member must use generic selpercatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

14. Request meets one of the following (a, b, or c):* a. Weight < 50 kg: Dose does not exceed both (i and ii): i. 240 mg per day; ii. 4 capsules per day; b. Weight ≥ 50 kg: Dose does not exceed both (i and ii): i. 320 mg per day; ii. 4 capsules per day; Page 3 of 8

    CLINICAL POLICY Selpercatinib 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/HIM – 6 months Commercial – 12 months or duration of request, whichever is less E. 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.
    II. Continued Therapy A. All Indications in Section I (must meet all):
17. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Retevmo for a covered indication and has received this medication for at least 30 days;

18. Member is responding positively to therapy;

    3. Retevmo is not prescribed concurrently with Gavreto;
    4. Member has not received prior RET targeted therapy (e.g., Gavreto);
    5. For brand Retevmo requests, member must use generic selpercatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
    6. If request is for a dose increase, request meets one of the following (a, b, or c): a. Weight < 50 kg: Dose does not exceed both (i and ii): i. 240 mg per day; ii. 4 capsules per day; b. Weight ≥ 50 kg: Dose does not exceed both (i and ii): i. 320 mg per day; ii. 4 capsules per day; 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/HIM – 12 months Page 4 of 8

    CLINICAL POLICY Selpercatinib Commercial – 12 months or duration of request, whichever is less
    B. Other diagnoses/indications (must meet 1 of 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 ATC: Anaplastic thyroid carcinoma DTC: differentiated thyroid carcinoma FDA: Food and Drug Administration MTC: medullary thyroid cancer Appendix B: Therapeutic Alternatives
    Not applicable NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer RET: rearranged during transfection Appendix C: Contraindications/Boxed Warnings None reported
    Appendix D: Examples of RET Fusion-Positive Solid Tumors RET fusion-positive solid tumor types evaluated in the LIBRETTO-001 clinical study (NCT03157128) included: • Pancreatic adenocarcinoma • Colorectal • Salivary
    • Breast • Sarcoma (soft tissue) • Xanthogranuloma • Carcinoid (bronchial) • Carcinoma of the skin Page 5 of 8

    CLINICAL POLICY Selpercatinib • Cholangiocarcinoma • Ovarian • Pulmonary carcinosarcoma V. Dosage and Administration
    • Rectal neuroendocrine • Small intestine Dosing Regimen Weight < 50 kg: 120 mg PO BID Weight ≥ 50 kg: 160 mg PO BID Maximum Dose Weight < 50 kg: 240 mg/day Weight ≥ 50 kg: 320 mg/day Indication NSCLC, thyroid cancer, RET fusion- positive solid tumors
    VI. Product Availability
    Capsules: 40 mg, 80 mg VII.