Last Review Date: 09/04/2025

Date of Origin: 11/05/2024

Dates Reviewed: 11/2024, 06/2025, 09/2025

1. Length of Authorization

• Initial: Prior authorization validity will be provided initially for 6 months.
• Renewal: Prior authorization validity may be renewed every 6 months thereafter.

2.  Dosing Limits

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

• First Dose:
  • 1000 billable units for one dose
• Subsequent Doses:
  • 1500 billable units every 42 days

3. Initial Approval Criteria ¹

Prior authorization validity is provided in the following conditions:

• Patient is at least 18 years of age; AND
• Patient is not experiencing Grade 2 or greater nausea and/or vomiting prior to the first infusion; AND

Universal Criteria ¹

• Patient does not have a complete or partial gastric outlet syndrome; AND
• Patient does not have a history of central nervous system metastases; AND

Gastric, Esophageal, and Gastro-Esophageal Junction (GEJ or EGJ) Cancers † ‡ Ф ^1-5

• Patient is not a surgical candidate or has locally advanced unresectable, recurrent, or metastatic adenocarcinoma; AND
• Used as first-line therapy; AND
• Patient has claudin (CLDN) 18.2-positive (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining) disease as determined by an FDA-approved or CLIA-compliant testv; AND
• Patient has human epidermal growth factor receptor 2 (HER2)-negative disease; AND
• Used in combination with a fluoropyrimidine- and platinum-containing chemotherapy-based regimen

v If confirmed using an immunotherapy assay-http://www.fda.gov/companiondiagnostics

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

4. Renewal Criteria ^1,3,13

Prior authorization validity may be renewed based upon 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
• 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 hypersensitivity reactions including anaphylaxis, severe nausea and vomiting, etc.

5. Dosage/Administration ^{1,13-15,17,18,20}

6. Billing Code/Availability Information

HCPCS Code:

• J1326 – Injection, zolbetuximab-clzb, 2 mg; 1 billable unit = 2 mg

NDC(s):

• Vyloy 100 mg powder in a single-dose vial: 00469-3425-xx
• Vyloy 300 mg powder in a single-dose vial: 0469-4425-xx

7. References

1. Vyloy [package insert]. Northbrook, IL; Astellas Pharma US, Inc.; June 2025. Accessed August  2025.
2. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for zolbetuximab. National Comprehensive Cancer Network, 2025. 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 2025.
3. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for Gastric Cancer, Version 2.2025. National Comprehensive Cancer Network, 2025. 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 2025.
4. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for Esophageal and Esophagogastric Junction Cancers, Version 3.2025. National Comprehensive Cancer Network, 2025. 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 2025.
5. Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab + mFOLFOX6 as first-line (1L) treatment for patients (pts) withclaudin-18.2+ (CLDN18.2+) / HER2− locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary results from phase 3 SPOTLIGHT study. JCO 41, LBA292-LBA292(2023). DOI:10.1200/JCO.2023.41.4_suppl.LBA292
6. Shah MA, Ajani JA, Al-Batran SE, et al. Zolbetuximab + CAPOX versus CAPOX in first-line treatment of claudin18.2+/HER2– advanced/metastatic gastric or gastroesophageal junction adenocarcinoma: GLOW phase 3 study.. JCO 40, TPS365-TPS365(2022). DOI:10.1200/JCO.2022.40.4_suppl.TPS365

Appendix A – Non-Quantitative Treatment Limitations (NQTL) Factor Checklist

Non-quantitative treatment limitations (NQTLs) refer to the methods, guidelines, standards of evidence, or other conditions that can restrict how long or to what extent benefits are provided under a health plan. These may include things like utilization review or prior authorization. The utilization management NQTL applies comparably, and not more stringently, to mental health/substance use disorder (MH/SUD) Medical Benefit Prescription Drugs and medical/surgical (M/S) Medical Benefit Prescription Drugs. The table below lists the factors that were considered in designing and applying prior authorization to this drug/drug group, and a summary of the conclusions that Prime’s assessment led to for each.

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