IMFINZI, Durvalumab Form

Durvalumab (Imfinzi®) is a programmed death-ligand 1 (PD-L1) blocking antibody. FDA Approved Indication(s) Imfinzi is indicated: • For the treatment of adult patients with unresectable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. In combination with tremelimumab-actl (Imjudo®) and platinum-based chemotherapy, for the treatment of adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
In combination with etoposide and either carboplatin or cisplatin as first-line treatment of adults patients with extensive-stage small cell lung cancer (ES-SCLC). In combination with gemcitabine and cisplatin, as treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). In combination with tremelimumab-actl (Imjudo®) for the treatment of adults patients with unresectable hepatocellular carcinoma (uHCC).
• • • • 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 Imfinzi 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 NSCLC;

   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Request meets one of the following (a, b, or c): a. Disease is unresectable, stage II-III, and has not progressed following concurrent platinum-based chemotherapy and radiation therapy (RT); b. Disease is recurrent, advanced, or metastatic with neither sensitizing EGFR mutations, ALK genomic tumor aberrations, or negative for other actionable molecular biomarkers (e.g., KRAS, ROS1, BRAF, NTRK1/2/3, MET, RET, Page 1 of 11

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   Durvalumab ERBB2 (HER2)) and is prescribed in combination with Imjudo (tremelimumab- actl) and platinum-based chemotherapy as first-line therapy (Appendix E); c. Continuation maintenance therapy for recurrent, advanced, or metastatic disease that is negative for actionable molecular biomarkers and no contraindications to PD-1 or PD-L1 inhibitors (see Appendix D), and performance status 0-2, that achieved tumor response or stable disease following initial systemic therapy with one of the following (i or ii): i. Imfinzi/Imjudo/pemetrexed with either carboplatin or cisplatin for nonsquamous cell histology, and Imfinzi for maintenance therapy is prescribed in combination with pemetrexed (off-label); ii. Imfinzi/Imjudo plus chemotherapy, and Imfinzi for maintenance therapy is prescribed a single agent (off-label);

2. Request meets one of the following (a, b, or c): a. For unresectable, stage II-III disease (i or ii):
   i. For body weight < 30 kg: dose does not exceed 10 mg/kg every 2 weeks; ii. For body weight ≥ 30 kg: dose does not exceed 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks; b. For metastatic disease (i or ii):
   i. For body weight < 30 kg: dose does not exceed Imfinzi 20 mg/kg every 3 weeks in combination with tremelimumab-actl 1 mg/kg and platinum-based chemotherapy, and then Imfinzi 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of Imjudo 1 mg/kg in combination with Imfinzi dose 6 at Week 16; ii. For body weight ≥ 30 kg: dose does not exceed Imfinzi 1,500 mg every 3 weeks in combination with tremelimumab-actl 75 mg and platinum-based chemotherapy for 4 cycles, and then Imfinzi 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed maintenance therapy every 4 weeks, and a fifth dose of Imjudo 75 mg in combination with Imfinzi dose 6 at Week 16; 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: 6 months B. Extensive-Stage Small Cell Lung Cancer (must meet all):
3. Diagnosis of ES-SCLC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed as first-line treatment with etoposide and either carboplatin or cisplatin, followed by maintenance with Imfinzi as a single agent;

4. Request meets one of the following (a, b, or c):* a. For body weight < 30 kg: dose does not exceed 20 mg/kg every 3 weeks in combination with chemotherapy for 4 cycles, then 10 mg/kg every 2 weeks as a single agent;
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   Durvalumab b. For body weight ≥ 30 kg: dose does not exceed 1,500 mg every 3 weeks in combination with chemotherapy for 4 cycles, then 1,500 mg every 4 weeks as a single agent; 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: 6 months C. Biliary Tract Cancer (must meet all):

5. Diagnosis of locally advanced, unresectable, recurrent (> 6 months after surgery and/or completion of adjuvant therapy), or metastatic BTC;
6. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with gemcitabine and cisplatin;
   5. Request meets one of the following (a, b, or c): a. For body weight < 30 kg: dose does not exceed 20 mg/kg every 3 weeks in combination with chemotherapy, then 20 mg/kg every 4 weeks as a single agent;
      b. For body weight ≥ 30 kg: dose does not exceed 1,500 mg every 3 weeks in combination with chemotherapy, then 1,500 mg every 4 weeks as a single agent; 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: 6 months D. Hepatocellular Carcinoma (must meet all):
7. Diagnosis of unresectable, liver-confined, or metastatic hepatocellular carcinoma;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Request meets one of the following (a, b, or c): a. For body weight < 30 kg: dose does not exceed Imfinzi 20 mg/kg in combination with tremelimumab-actl 4 mg/kg as a single dose at Cycle 1/Day 1, followed by Imfinzi as a single agent every 4 weeks; b. For body weight ≥ 30 kg: dose does not exceed Imfinzi 1,500 mg in combination with tremelimumab-actl 300 mg as a single dose at Cycle 1/Day 1, followed by Imfinzi as a single agent every 4 weeks; c. Dose 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 E. Cervical Cancer (off-label) (must meet all):
8. Diagnosis of persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC);

9. Prescribed by or in consultation with an oncologist;

   3. Age ≥ 18 years;
   4. Prescribed in combination with etoposide and either cisplatin or carboplatin;
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   Durvalumab

10. Request meets one of the following (a or b): a. Dose does not exceed the FDA approved maximum recommended dose; b. Dose 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 F. 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 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.
    II. Continued Therapy A. All Indications in Section I (must meet all):
13. Currently receiving medication via Centene benefit, or member has previously met initial approval criteria, or documentation supports that member is currently receiving Imfinzi for a covered indication and has received this medication for at least 30 days;
14. For stage II-III NSCLC requests, member has not received more than 12 months of Imfinzi therapy;

15. Member is responding positively to therapy;

    4. If request is for a dose increase, request meets one of the following (a, b, c, d, e, or f):* a. For stage II-III NSCLC (i or ii): i. For body weight < 30 kg: new dose does not exceed 10 mg/kg every 2 weeks; ii. For body weight ≥ 30 kg: new dose does not exceed 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks b. For metastatic NSCLC (i or ii): i. For body weight < 30 kg: new dose does not exceed Imfinzi 20 mg/kg every 3 weeks in combination with tremelimumab-actl and platinum-based chemotherapy for 4 cycles, then Imfinzi 20 mg/kg every 4 weeks with histology-based pemetrexed maintenance therapy; Page 4 of 11

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    Durvalumab ii. For body weight ≥ 30 kg: new dose does not exceed Imfinzi 1,500 mg every 3 weeks in combination with tremelimumab-actl and platinum based chemotherapy for 4 cycles, then Imfinzi 1,500 mg every 4 weeks with histology-based pemetrexed maintenance therapy; c. For ES-SCLC (i or ii): i. For body weight < 30 kg: new dose does not exceed 20 mg/kg every 3 weeks in combination with chemotherapy for 4 cycles, then 10 mg/kg every 2 weeks as a single agent;
    ii. For body weight ≥ 30 kg: new dose does not exceed 1,500 mg every 3 weeks in combination with chemotherapy for 4 cycles, and then 1,500 mg every 4 weeks as a single agent; d. For BTC (i or ii): i. For body weight < 30 kg: new dose does not exceed 20 mg/kg every 3 weeks in combination with chemotherapy, then 20 mg/kg every 4 weeks as a single agent;
    ii. For body weight ≥ 30 kg: new dose does not exceed 1,500 mg every 3 weeks in combination with chemotherapy, then 1,500 mg every 4 weeks as a single agent; e. uHCC (i or ii):
    i. For body weight < 30 kg: new dose does not exceed 20 mg/kg in combination with tremelimumab-actl, then 20mg/kg every 4 weeks;
    ii. For body weight ≥ 30 kg: new dose does not exceed, 1,500 mg in combination with tremelimumab-actl, then 1,500 mg every 4 weeks; f. 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:
    Stage II-III NSCLC: up to a total duration of 12 months All other indications: 12 months B. Other diagnoses/indications (must meet 1 or 2):

16. 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

17. 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 Page 5 of 11

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    Durvalumab 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 ALK: anaplastic lymphoma kinase BTC: biliary tract cancer ES-SCLC: extensive-stage small cell lung cancer EGFR: epidermal growth factor receptor FDA: Food and Drug Administration NECC: neuroendocrine carcinoma of the cervix NSCLC: non-small cell lung cancer PD-L1: programmed death-ligand RT: radiotherapy
    uHCC: unresectable hepatocellular carcinoma 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 Dose Limit/ Maximum Dose Varies
    NSCLC (examples of concurrent platinum-containing/radiotherapy regimens) cisplatin, etoposide, RT carboplatin/cisplatin, pemetrexed, RT paclitaxel, carboplatin, RT ES-SCLC (regimen examples as included in the NCCN SCLC guidelines) (carboplatin or cisplatin) and etoposide and Imfinzi See dosing regimens Varies Carboplatin AUC 5-6 day 1 and etoposide 80-100 mg/m2 days 1, 2, 3 and Imfinzi 1,500 mg day 1 every 21 days x 4 cycles followed by maintenance Imfinzi 1,500 mg day 1 every 28 days Cisplatin 75-80 mg/m2 day 1 and etoposide 80-100 mg/m2 days 1, 2, 3 and Imfinzi 1,500 mg day 1 every 21 days x 4 cycles followed by maintenance Imfinzi 1,500 mg day 1 every 28 days 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. Page 6 of 11

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    Durvalumab Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • On February 22, 2021, AstraZeneca announced the voluntary withdrawal of the indication for Imfinzi for second-line treatment of locally advanced or metastatic bladder cancer. Imfinzi was approved for this indication under the accelerated pathway in 2017, based on study results that showed positive tumor response rates and duration of response. In its announcement, AstraZeneca pointed to results from the DANUBE confirmatory trial, in which Imfinzi failed to meet its key primary endpoint of overall survival. • Actionable molecular biomarkers include EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, and ERBB2 (HER2). If there is insufficient tissue to allow testing for all of EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, and ERBB2 (HER2), repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes. • Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, and some oncogenic drivers (i.e., EGFR exon 19 deletion or exon 21 L858R, ALK rearrangements) have been shown to be associated with less benefit from PD-1/PD- L1 inhibitors. Appendix E: Recommended Combination Regimens Tumor Histology Non- Squamous Imfinzi Dosage 1,500 mg 75 mg Patient Weight ≥ 30 kg Tremelimumab- actl Dosage < 30 kg 20 mg/kg 1 mg/kg Squamous ≥ 30 kg 1,500 mg 75 mg < 30 kg 20 mg/kg 1 mg/kg Platinum-based Chemotherapy Regimen carboplatin & nab-paclitaxel OR carboplatin or cisplatin & pemetrexed carboplatin & nab-paclitaxel OR carboplatin or cisplatin & gemcitabine V. Dosage and Administration
    Indication Dosing Regimen NSCLC Stage II-III: • Weight ≥ 30 kg: 10 mg/kg IV every 2 weeks or 1,500 mg every 4 weeks • Weight < 30 kg: 10 mg/kg IV every 2 weeks Metastatic: • Weight ≥ 30 kg: 1,500 mg every 3 weeks in combination with tremelimumab-actl 75 mg and Maximum Dose Stage II-III See regimen; maximum duration of 12 months Metastatic: See regimen Page 7 of 11

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    Durvalumab Indication Dosing Regimen Maximum Dose platinum-based chemotherapy for 4 cycles, and then administer Imfinzi 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed maintenance therapy every 4 weeks, and a fifth dose of tremelimumab-actl 75 mg in combination with Imfinzi dose 6 at week 16 • Weight < 30 kg: 20 mg/kg every 3 weeks in combination with tremelimumab-actl 1 mg/kg and platinum-based chemotherapy, and then administer Imfinzi 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of tremelimumab-actl 1 mg/kg in combination with Imfinzi dose 6 at week 16 • Weight ≥ 30 kg: 1,500 mg IV in combination with chemotherapy † every 3 weeks (21 days) for 4 cycles, followed by 1,500 mg every 4 weeks as a single agent • Weight < 30 kg: 20 mg/kg IV in combination with chemotherapy* every 3 weeks (21 days) for 4 cycles, following by 10 mg/kg every 2 weeks as a single agent
    See regimen ES-SCLC BTC • Weight ≥ 30 kg: 1,500 mg IV every 3 weeks in See regimen uHCC combination with chemotherapy †, then 1,500 mg every 4 weeks as a single agent • Weight < 30 kg: 20 mg/kg IV every 3 weeks in combination with chemotherapy †, then 20 mg/kg every 4 weeks as a single agent • Weight ≥ 30 kg: Imfinzi 1,500 mg in combination with tremelimumab-actl (Imjudo) 300 mg as a single dose at Cycle 1/Day 1, followed by Imfinzi as a single agent every 4 weeks • Weight < 30 kg: Imfinzi 20 mg/kg in combination with tremelimumab-actl (Imjudo) 4 mg/kg as a single dose at Cycle 1/Day 1, followed by Imfinzi as a single agent every 4 weeks See regimen

    • Optional pemetrexed therapy may be initiated from week 12 until disease progression or intolerable toxicity for patients with nonsquamous disease who received treatment with pemetrexed and carboplatin/cisplatin. †Administer Imfinzi prior to chemotherapy on the same day. Refer to the Prescribing Information for the agent administered in combination with Imfinzi for recommended dosage information, as appropriate. [For ES-SCLC, see also Appendix B. Therapeutic Alternatives for NCCN regimens as carboplatin, cisplatin, and etoposide are off-label for this indication.] Page 8 of 11

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    Durvalumab VI. Product Availability
    Single-dose vials: 120 mg/2.4 mL, 500 mg/10 mL
    VII.