Last Review Date: 03/05/2024

Date of Origin: 03/31/2023

Dates Reviewed: 04/2023, 09/2023, 12/2023, 03/2024

1. Length of Authorization ^{Δ 1}

Coverage will be provided for 6 months and may be renewed. Coverage can be authorized up to a maximum of 24 months (26 total doses) of therapy.

2. Dosing Limits

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

• Zynyz 500 mg/20 mL single-dose vial: 1 vial every 4 weeks

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

• Anal Carcinoma & Merkel Cell Carcinoma: 500 billable units every 4 weeks

3. Initial Approval Criteria ^1,2

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ^1,2

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

Anal Carcinoma ‡ ^2,9,10

• Used as subsequent therapy for metastatic disease

Merkel Cell Carcinoma (MCC) † ‡ Ф ^1-4

• Patient has metastatic or recurrent locally advanced disease †; OR
• Patient has primary locally advanced disease; AND
  • Both curative surgery and curative radiation therapy are not feasible; OR
  • Patient has had disease progression on neoadjuvant nivolumab therapy; OR
• Patient has recurrent regional disease; AND
  •  Both curative surgery and curative radiation therapy are not feasible

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

4. Renewal Criteria ^{Δ 1}

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion-related reactions, severe immune-mediated adverse reactions (e.g., pneumonitis, hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions/rash, etc.), complications of allogeneic hematopoietic stem cell transplantation (HSCT), solid organ transplant rejection, etc.; AND
• Patient has not exceeded a maximum of twenty-four (24) months of therapy

5. Dosage/Administration ^{Δ 1,10}

6. Billing Code/Availability Information

HCPCS Code:

• J9345 – Injection, retifanlimab-dlwr, 1 mg; 1 billable unit = 1 mg

NDC:

• Zynyz 500 mg/20 mL solution in a single-dose vial: 50881-0006-xx

7. References

1. Zynyz [package insert]. Wilmington, DE; Incyte, Inc.; November 2023. Accessed January 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) retifanlimab-dlwr. 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 January 2024.
3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Merkel Cell Carcinoma. 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 January 2024.
4. Grignani G, Rutkowski P, Lebbé C. A Phase 2 Study of Retifanlimab in Patients With Advanced or Metastatic Merkel Cell Carcinoma (POD1UM-201)
4. Presented at the Society for Immunotherapy of  Cancer’s 36th Annual Meeting Washington, DC • November 10–14, 2021 [Epub ahead of print]
5. Gupta S, Sonpavde G, Grivas P, et al. Defining “platinum-ineligible” patients with metastatic urothelial cancer (mUC). J Clin Oncol. 2019 Mar 1;37(7_suppl):451.
6. Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.
7. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf
8. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
9. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Anal Cell Carcinoma. 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 January 2024.
10. Rao S, Anandappa G, Capdevila J, et al. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202). ESMO Open. 2022 Aug;7(4):100529. doi: 10.1016/j.esmoop.2022.100529. Epub 2022 Jul 8. PMID: 35816951; PMCID: PMC9463376.

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