Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) Form

Lutetium Lu 177 vipivotide tetraxetan (Pluvicto ™) is a radioligand therapeutic agent. FDA Approved Indication(s) Pluvicto is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy. 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 Pluvicto is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Metastatic Castration-resistant Prostate Cancer (must meet all):

1. Diagnosis of metastatic CRPC;
   2. Documentation of disease progression despite bilateral orchiectomy or other androgen deprivation therapy (ADT) (see Appendix D);
2. Documentation of PSMA-positive disease confirmed on a GA-PSMA-11 or piflufolastat F-18 positive emission tomography (PET) or computed tomography (CT) scan;
3. Prescribed by or in consultation with an oncologist or urologist;
   
   5. Age ≥ 18 years;
   6. Member will use a gondatropin-releasing hormone (GnRH) analog concurrently or has had a bilateral orchiectomy;
4. Failure of both of the following, unless contraindicated or clinically significant adverse effects are experienced or all are contraindicated (a and b): a. A taxane-based regimen (e.g. docetaxel, cabazitaxel);Prior authorization may be required for docetaxel and cabazitaxel b. Abiraterone (Zytiga®), unless member has previously failed Yonsa® (abiraterone) or Xtandi® (enzalutamide);Prior authorization may be required for Zytiga, Yonsa, and Xtandi

5. Pluvicto is not prescribed concurrently with cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy;
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   CLINICAL POLICY Lutetium Lu 177 vipivotide tetraxetan

6. Request meets one of the following (a or b): a. Dose does not exceed 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses; 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: 6 months (up to a total of 6 doses) B. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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. Metastatic Castration-resistant Prostate Cancer (must meet all):
9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Pluvicto for a covered indication and has received this medication for at least 30 days;
10. Member is responding positively to therapy;
    3. Member has not received ≥ 6 doses (infusions) of Pluvicto;
    4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses; 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: 6 months (up to a total of 6 doses) 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): 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 Page 2 of 7

    CLINICAL POLICY Lutetium Lu 177 vipivotide tetraxetan 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

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, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. Approval duration: Duration of request or 6 months (whichever is less) 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 ADT: androgen deprivation therapy AR: androgen receptor BSoC: best standard of care
    CRPC: castration- resistant prostate cancer
    CT: computed tomography FDA: Food and Drug Administration GnRH: gondatropin-releasing hormone LHRH: luteinizing hormone-releasing hormone NCCN: National Comprehensive Cancer Network
    PET: positive emission tomography PSMA: prostate- specific membrane antigen 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.
    Dosing Regimen Drug Name abiraterone (Zytiga®) docetaxel 1,000 mg PO QD (given in combination with prednisone)
    Androgen-deprivation therapy with docetaxel 75 mg/m2 for 6 cycles 20 mg/m2 IV every 3 weeks
    Jevtana® (cabazitaxel)
    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. 25 mg/m2 once every 3 weeks Dose Limit/ Maximum Dose 1,000 mg/day; 2,000 mg/day if taking a strong CYP3A4 inducer
    Varies Appendix C: Contraindications/Boxed Warnings None reported
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    CLINICAL POLICY Lutetium Lu 177 vipivotide tetraxetan Appendix D: General Information
    • Castration-resistant prostate cancer is prostate cancer that progresses clinically, radiographically, or biochemically despite castrate levels of serum testosterone (< 50 ng/dL).
    • Per the NCCN, androgen deprivation therapy (ADT) should be continued in patients with metastatic CRPC while additional therapies, including secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies are applied.
    • Examples of ADT include: o Bilateral orchiectomy (surgical castration) o Luteinizing hormone-releasing hormone (LHRH) agonist given with or without an anti-androgen:  LHRH agonists: Zoladex® (goserelin), leuprolide (Lupron Depot®, Eligard®), and Trelstar® (triptorelin)  Anti-androgens: bicalutamide (Casodex®), flutamide (Eulexin®), nilutamide (Nilandron®), Xtandi® (enzalutamide), Erleada® (apalutamide), Nubeqa® (darolutamide) o LHRH antagonist: Firmagon® (degarelix), Orgovyx® (relugolix) V. Dosage and Administration
    Indication Metastatic CRPC Dosing Regimen 7.4 GBq (200 mCi) IV every 6 weeks for up to 6 doses Maximum Dose See dosing regimen VI. Product Availability
    Injection, single-dose vial: 1,000 MBq/mL (27 mCi/mL)
    VII.