Last Review Date: 10/03/2024

Date of Origin: 10/30/2018

Dates Reviewed: 11/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 6/2020, 12/2020, 03/2021, 06/2021, 09/2021, 12/2021, 03/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024, 07/2024, 10/2024

1. Length of Authorization ^{Δ 1,12,14}

Coverage will be provided for 6 months and may be renewed, unless otherwise specified.

• Neoadjuvant therapy in Cutaneous Squamous Cell Carcinoma (cSCC) can be authorized up to a maximum of 4 doses and cannot be renewed.
• Treatment for metastatic, locally advanced, or recurrent cSCC, and Basal Cell Carcinoma (BCC) can be renewed up to a maximum of twenty-four (24) months of therapy (35 doses).
• Treatment for recurrent or metastatic Cervical Cancer, recurrent or metastatic Vaginal Cancer and advanced, recurrent or metastatic Vulvar Cancer can be authorized up to a maximum of ninety-six (96) weeks of therapy (32 doses).

2. Dosing Limits

• Quantity Limit (max daily dose) [NDC Unit]:

• Libtayo 350 mg/7 mL single-dose vial: 1 vial per 21 days

• Max Units (per dose and over time) [HCPCS Unit]:

All Indications –

2. • 350 billable units (350 mg) every 21 days
3. Initial Approval Criteria ¹

Coverage is provided for the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ¹

• Patient has not received previous therapy with a programmed death (PD-1/PD-L1)-directed therapy (e.g., avelumab, pembrolizumab, atezolizumab, durvalumab, nivolumab, dostarlimab, nivolumab/relatlimab, retifanlimab, tislelizumab, toripalimab, etc.), unless otherwise specified ^Δ; AND

Cutaneous Squamous Cell Carcinoma (cSCC) † ‡ ^1-5,8,12

• Used as a single agent; AND
  • Patient has metastatic, locally advanced, or recurrent disease ^Δ; AND
    • Patient is not a candidate for curative surgery or curative radiation therapy; OR
  • Used as neoadjuvant therapy; AND
    • Patient has borderline resectable disease, unresectable disease, or surgery may carry a high morbidity; OR
    • Used for one of the following:
      • Tumor has very rapid growth
      • In-transit metastasis
      • Lymphovascular invasion
      • Surgery alone may not be curative or may result in significant functional limitation; AND

• • • Patient has very high-risk disease*; OR
    • Patient has locally advanced disease

* Very High-Risk features include preoperative clinical tumor diameter >4 cm, poor differentiation, desmoplastic disease, thickness or level of invasion is >6 mm or invasion beyond subcutaneous fat, tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring ≥0.1 mm, lymphatic or vascular involvement

Cervical Cancer ‡ ^2,14

• Used as a single agent as subsequent therapy; AND
• Patient has recurrent or metastatic disease ^Δ

Basal Cell Carcinoma (BCC) † ‡ ^1,2,6,9,13

• Used as a single agent; AND
  • Patient has locally advanced or metastatic disease ^Δ; OR
  • Patient has nodal disease and surgery is not feasible ^Δ

Non-Small Cell Lung Cancer (NSCLC) † ‡ ^{1,2,7,10,15,16}

• Patient has recurrent, advanced, or metastatic disease (excluding locoregional recurrence or symptomatic local disease with no evidence of disseminated disease) or mediastinal lymph node recurrence with prior radiation therapy; AND
  • Used in combination with platinum‐based chemotherapy (e.g., paclitaxel and either carboplatin or cisplatin OR pemetrexed and either carboplatin or cisplatin); AND
    • • Used as first-line therapy for one of the following:

• • • • Patients with a performance status (PS) 0-1 who have tumors that are negative for actionable molecular biomarkers* ¥ and PD-L1 expression <1%
      • Patients with a PS 0-1 who are positive for one of the following molecular biomarkers: EGFR exon 20, BRAF V600E, NTRK1/2/3 gene fusion, MET exon 14 skipping, RET rearrangement, or ERBB2 (HER2)
      • PD-L1 expression-positive (PD-L1 ≥1%) tumors that are negative for actionable molecular biomarkers* ¥; OR

• • • • Used as subsequent therapy for one of the following:

• • • • Patients with a PS 0-1 who are positive for one of the following molecular biomarkers and have received prior targeted therapy§: EGFR exon 19 deletion or exon 21 L858R tumors, EGFR S768I, L861Q, and/or G719X, ALK rearrangement, or ROS1 rearrangement
      • Patients with a PS 0-1 who are positive for one of the following molecular biomarkers: BRAF V600E, NTRK1/2/3 gene fusion, MET exon 14 skipping, or RET rearrangement; OR
  • Used in combination with pemetrexed; AND
    • Used as continuation maintenance therapy in patients who have achieved a tumor response or stable disease after first-line therapy with cemiplimab, pemetrexed, and either carboplatin or cisplatin for non-squamous cell histology; OR
  • Used as a single agent; AND
    • Patient has tumors that are negative for actionable molecular biomarkers* ¥ and high PD-L1 expression (Tumor Proportion Score [TPS] ≥ 50%) as determined by an FDA-approved or CLIA compliant testv; AND
      • Used as first-line therapy †; OR
      • Used as continuation maintenance therapy in patients who achieved a tumor response or stable disease after first-line therapy with cemiplimab as monotherapy or as part of combination therapy; OR
    • Patient has tumors with PD-L1 expression <1% or ≥1%-49%; AND
      • Used as continuation maintenance therapy in patients who have achieved a tumor response or stable disease following initial therapy with cemiplimab combination therapy

Vaginal Cancer ‡ ^2,14

• Used as a single agent as subsequent therapy; AND
• Patient has recurrent or metastatic disease ^Δ

Vulvar Cancer ‡ ^2,4,14

• Used as a single agent as subsequent therapy; AND
• Patient has advanced or recurrent/metastatic disease ^Δ

v If confirmed using an FDA approved assay – http://www.fda.gov/companiondiagnostics

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^{Δ 1,12}

Coverage may be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion-related reactions, severe and fatal immune-mediated adverse reactions (e.g., pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, etc.), complications of allogeneic hematopoietic stem cell transplantation (HSCT), etc.; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND

Non-Small Cell Lung Cancer (continuation maintenance therapy):

• Refer to Section III for criteria

Cutaneous Squamous Cell Carcinoma (cSCC) (neoadjuvant therapy):

• Coverage may not be renewed

Cutaneous Squamous Cell Carcinoma (cSCC) (metastatic, locally advanced, or recurrent disease)

• Patient has not exceeded a maximum of twenty-four (24) months of therapy

Cervical Cancer

• Patient has not exceeded a maximum of ninety-six (96) weeks of therapy

Basal Cell Carcinoma

• Patient has not exceeded a maximum of twenty-four (24) months of therapy

Vaginal Cancer

• Patient has not exceeded a maximum of ninety-six (96) weeks of therapy

Vulvar Cancer

• Patient has not exceeded a maximum of ninety-six (96) weeks of therapy

5. Dosage/Administration ^{Δ 1,12,14}

6.  Billing Code/Availability Information

HCPCS Code:

• J9119 − Injection, cemiplimab-rwlc, 1 mg; 1 billable units = 1 mg

NDC:

• Libtayo 350 mg/7 mL single-dose vial: 61755-0008-xx

7. References

1. Libtayo [package insert]. Tarrytown, NY; Regeneron Pharmaceuticals; April 2024. Accessed August 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) cemiplimab-rwlc. National Comprehensive Cancer Network, 2024.  The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed August 2024.
3. Falchook GS, Leidner R, Stankevich E, et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer. 2016 Nov 15;4:70. doi: 10.1186/s40425-016-0176-3. eCollection 2016.
4. Migden MR, Rischin D, Schmults CD, et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-351. doi: 10.1056/NEJMoa1805131. Epub 2018 Jun 4.
5. Migden MR, Khushalani NI, Chang ALS, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020 Feb;21(2):294-305. doi: 10.1016/S1470-2045(19)30728-4. Epub 2020 Jan 14.
6. Lewis KD, Fury MG, Stankevich, et al. Phase II study of cemiplimab, a human monoclonal anti-PD-1, in patients with advanced basal cell carcinoma (BCC) who experienced progression of disease on, or were intolerant of prior hedgehog pathway inhibitor (HHI) therapy. Annals of Oncology. 2018 Oct 01; Volume 29, Supplement 8,VII440.
7. Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021 Feb 13;397(10274):592-604.
8. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Squamous Cell Skin Cancer. Version 1.2024. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed August 2024.
9. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Basal Cell Skin Cancer. Version 3.2024. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed August 2024.
10. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Non-Small Cell Lung Cancer. Version 9.2024. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed September 2024.

11. Gogishvili M, Melkadze T, Makharadze T, et al. LBA51 EMPOWER-Lung 3: Cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC). Annals of Oncology, ISSN: 0923-7534, Vol: 32, SUPPLEMENT 5, S1328, SEPTEMBER 01, 2021. DOI10.1016/j.annonc.2021.08.2130.
12. Gross N, Miller D, Khushalani N, et al. Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma N Engl J Med 2022; 387:1557-1568. doi: 10.1056/NEJMoa2209813
13. Stratigos AJ, Sekulic A, Peris K, et al. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol 2021;22:848-857.
14. Tewari KS, Monk BJ, Vergote I, et al. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med 2022;386:544-555.
15. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022 Nov;28(11):2374-2380. doi: 10.1038/s41591-022-01977-y. Epub 2022 Aug 25. PMID: 36008722; PMCID: PMC9671806.
16. Özgüroğlu M, Kilickap S, Sezer A, et al. First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2023; 24: 989–1001.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A