Clinical Policy: Retifanlimab-dlwr (Zynyz)

Reference Number: CP.PHAR.629
Effective Date: 06.01.23
Last Review Date: 05.26
Line of Business: Commercial, HIM/ICHRA, Medicaid

[Coding Implications](Coding Implications)
[Revision Log](Revision Log)

See [Important Reminder](Important Reminder) at the end of this policy for important regulatory and legal information.

Description

Retifanlimab-dlwr (Zynyz®) is a programmed death receptor-1 (PD-1)-blocking antibody.

FDA Approved Indication(s)

Zynyz is indicated:

• In combination with carboplatin and paclitaxel for the first-line treatment of adult patients
  with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal
  (SCAC)
• As a single agent for the treatment of adult patients with locally recurrent or metastatic
  SCAC with disease progression on or intolerance to platinum-based chemotherapy
• For the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell
  carcinoma (MCC)

Policy/Criteria

*Prescribed regimen must be FDA-approved or recommended by NCCN

Clinical Policy

Retifanlimab-dlwr

Approval duration:

Medicaid/HIM/ICHRA– 12 months
Commercial – 6 months or to the member’s renewal date, whichever is longer

B. Anal Carcinoma (must meet all):

*Prescribed regimen must be FDA-approved or recommended by NCCN

Approval duration:

Medicaid/HIM/ICHRA– 12 months
Commercial – 6 months or to the member’s renewal date, whichever is longer

C. NCCN Recommended Uses (off-label) (must meet all):

1. Diagnosis of one of the following (a, b, c, or d):
   a. Appendiceal neoplasm or cancer;
   b. Colon cancer;
   c. Rectal cancer;
   d. Small bowel adenocarcinoma;
2. Disease is one of the following mutations (a, b, or c):
   a. Microsatellite instability-high (MSI-H);
   b. Deficient mismatch repair (dMMR);
   c. Polymerase epsilon/delta (POLE/POLD1) with ultra-hypermutated phenotype
   (e.g., tumor mutation burden [TMB] > 50 mut/Mb);
3. Prescribed by or in consultation with an oncologist;
4. Age ≥ 18 years;
5. Prescribed as a single agent;
6. Request meets one of the following (a or b):
   a. Dose does not exceed 500 mg (1 vial) every four weeks;
   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:

Medicaid/HIM/ICHRA– 12 months
Commercial – 6 months or to the member’s renewal date, whichever is longer

D. Other diagnoses/indications (must meet 1 or 2):

1. 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/ICHRA)
   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/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance
   marketplace/ICHRA) 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/ICHRA, and CP.PMN.16 for Medicaid; or
2. 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/ICHRA, and CP.PMN.53 for Medicaid.

Clinical Policy

Retifanlimab-dlwr

II. Continued Therapy

A. All Indications in Section I (must meet all):

1. Currently receiving medication via Centene benefit, or documentation supports that
   member is currently receiving Zynyz for a covered indication and has received this
   medication for at least 30 days;
2. Member is responding positively to therapy;
3. If request is for a dose increase, request meets one of the following (a or b):
   a. New dose does not exceed 500 mg (1 vial) every four weeks;
   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:

Medicaid/HIM/ICHRA– 12 months
Commercial – 6 months or to the member’s renewal date, whichever is longer

B. Other diagnoses/indications (must meet 1 or 2):

1. 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/ICHRA)
   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/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance
   marketplace/ICHRA) 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/ICHRA, and CP.PMN.16 for Medicaid; or
2. 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/ICHRA, and CP.PMN.53 for Medicaid.

Clinical Policy

Retifanlimab-dlwr

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/ICHRA, and
CP.PMN.53 for Medicaid or evidence of coverage documents.

IV. Appendices/General Information

Appendix A: Abbreviation/Acronym Key

FDA: Food and Drug Administration
MCC: Merkel cell carcinoma
NCCN: National Comprehensive Cancer
Network
SCAC: squamous cell carcinoma of the
anal canal

Appendix B: Therapeutic Alternatives

Not applicable

Appendix C: Contraindications/Boxed Warnings

None reported

V. Dosage and Administration

VI. Product Availability

Single-dose vial: 500 mg/20 mL (25 mg/mL)

2. National Comprehensive Cancer Network Drugs and Biologics Compendium. Available at:
   https://www.nccn.org/professionals/drug_compendium. Accessed January 28, 2026.
3. National Comprehensive Cancer Network. Merkel Cell Carcinoma Version 2.2026.
   Available at https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf. Accessed
   January 28, 2026.
4. National Comprehensive Cancer Network. Anal Carcinoma Version 1.2026. Available at
   https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf. Accessed January 28, 2026.

Coding Implications

Codes referenced in this clinical policy are for informational purposes only. Inclusion or
exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-
date sources of professional coding guidance prior to the submission of claims for
reimbursement of covered services.

Clinical Policy

Retifanlimab-dlwr

Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

Clinical Policy

Retifanlimab-dlwr