CurrentAnthemPolicy CC-0273

Vyloy (zolbetuximab-clzb) — Coverage Criteria

Criteria and coding governing prior authorization and medical necessity for Vyloy (zolbetuximab-clzb) for treatment of CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma, affecting providers submitting medical benefit requests to Anthem.

Policy Summary

PayerAnthem

PolicyVyloy (zolbetuximab-clzb) — Coverage Criteria

Policy CodePolicy CC-0273

Change TypeCoding and guideline update

Effective DateNov 14, 2025

Next Review Date

Key ActionObtain prior authorization and document CLDN18.2 positivity, HER2-negative status, first-line intent, planned combination chemotherapy, and ECOG performance status.

SourceLink

POLICY UPDATE CHANGES

Added NCCN category 1, 2A recommendation for use in palliative care of Gastric or GEJ cancers.

Updated HCPCS coding: removed C9303 effective 6/30/25 and added J1326 effective 7/1/25 for Vyloy.

First-lineIndicated line

≈38%CLDN18.2 expression

J1326Current HCPCS

ECOG 0-1Performance status

Coverage Criteria for Vyloy (zolbetuximab-clzb)

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Initial approval criteria (first-line CLDN18.2-positive gastric/GEJ adenocarcinoma)

Requests for Vyloy may be approved if ALL of the following are met (except where OR is specified):

Age: Individual is under 19 years of age; OR adult criteria apply

Policy includes an isolated clause for individuals under 19; adult clinical criteria follow

Diagnosis: Individual has a diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma

Supported by FDA label and NCCN

Disease and biomarker requirements: Tumor is CLDN18.2 positive AND disease is HER2-negative locally advanced unresectable or metastaticCLDN18.2 positive

VENTANA CLDN18 (43-14A) RxDx Assay is the companion diagnostic

Line and regimen: Using as first-line treatment AND in combination with fluoropyrimidine- and platinum-containing chemotherapy

Policy requires first-line use in combination with specified chemotherapy

Performance status: ECOG performance status 0 to 1 (primary) OR ECOG performance status 0 to 2 (alternate clause)ECOG 0-1 / 0-2

Both ECOG ranges are present in the policy criteria

Palliative / Resectability: Individual is not a surgical candidate OR has unresectable locally advanced, recurrent, or metastatic disease

One of these must be true for palliative intent per policy

Requests for Vyloy may be denied when specific clinical exclusions or limitations are present. The policy explicitly lists the following conditions as not meeting approval criteria: complete or partial gastric outlet syndrome with persistent or recurrent vomiting, a history of central nervous system metastases, or a history of carcinomatous meningitis from gastric/GEJ cancer. These exclusions are applied in addition to the core eligibility requirements (diagnosis, biomarker status, line of therapy, combination regimen, and performance status) and should be documented when present to avoid inappropriate authorization.

Use of Vyloy outside the defined population is not supported by this policy. Specifically, the policy requires tumors to be CLDN18.2 positive and disease to be HER2-negative in the specified gastric or gastroesophageal junction (GEJ) adenocarcinoma setting. Approval is limited to first-line treatment administered in combination with fluoropyrimidine- and platinum-containing chemotherapy for locally advanced unresectable or metastatic disease. Requests for tumors that are CLDN18.2 negative, HER2-positive, for non–first-line therapy, or for indications other than gastric/GEJ adenocarcinoma fall outside the scope of coverage under this policy.

Regimen	Indication / Line	Coverage
Vyloy (zolbetuximab-clzb) in combination with a fluoropyrimidine- and platinum-containing chemotherapy
First-line treatment of locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
Covered when all policy criteria are met (tumor CLDN18.2 positive, HER2-negative disease, first-line use in combination with fluoropyrimidine- and platinum-containing chemotherapy, ECOG 0–1 [alternate clause allows 0–2], and not meeting exclusions)

Provider Actions and Administrative Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Vyloy (zolbetuximab-clzb). Requests will be reviewed and approvals are contingent on meeting the clinical criteria in this policy (including diagnosis, CLDN18.2 positivity, HER2 status, ECOG performance status, line of therapy, and required regimen). Do not assume coverage without an approved prior authorization.

Prior authorization required before initiation of therapy
Approvals contingent on meeting all applicable clinical criteria in this policy
Denials may occur if documentation is incomplete or criteria are not met

Step Therapy

Step Therapy / First-line Use

There is no step therapy or requirement to try an alternative systemic therapy prior to initiation of Vyloy when the patient otherwise meets policy criteria. Vyloy is indicated as first-line therapy in combination with fluoropyrimidine- and platinum-containing chemotherapy for CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.

Documentation Required

Required Documentation

Providers must submit complete documentation with prior authorization requests. Include clinical and diagnostic evidence to demonstrate the member meets all required criteria.

Primary diagnosis (gastric or gastroesophageal junction adenocarcinoma) with relevant ICD-10 code(s)
CLDN18.2 test result and method (e.g., VENTANA CLDN18 (43-14A) RxDx Assay) confirming tumor is CLDN18.2 positive
HER2 status documentation showing HER2-negative disease
Planned regimen details showing combination with fluoropyrimidine- and platinum-containing chemotherapy and that use is first-line
Current ECOG performance status (0–1 for initial approval per criteria; some continuation language allows up to 2)
Documentation of extent of disease and rationale if unresectable or not a surgical candidate

Definitions

ECOG Performance Status — definition and policy ranges

Scale overviewECOG Performance Status is a 0–5 scale assessing functional status where 0 = fully active and 5 = dead

Primary policy requirementECOG 0–1 is required for approval (primary criteria)

Alternate allowanceAn ECOG performance status of 0–2 is referenced as an alternate clause permitting approval in specific circumstances

Common descriptorsExamples from the scale: 1 = restricted in strenuous activity but ambulatory; 2 = ambulatory and capable of all self-care but unable to work

CLDN18.2 — definition and companion diagnostic

Marker definitionClaudin18.2 (CLDN18.2) is a highly selective marker protein expressed in differentiated gastric mucosal membrane epithelial cells

Role in therapy selectionCLDN18.2 expression identifies tumors eligible for treatment with Vyloy (zolbetuximab-clzb)

Companion diagnostic noteThe VENTANA CLDN18 (43-14A) RxDx Assay is approved to identify CLDN18.2-positive gastric/GEJ adenocarcinomas

Revision History

2025-11-14revisionLatest

Annual review: added NCCN category 1 and 2A recommendation for palliative use in gastric or GEJ cancers; administrative update for age.

2025-05-28coding update

Removed HCPCS C9303 effective 2025-06-30 and added HCPCS J1326 effective 2025-07-01 for Vyloy.

2025-03-04coding update

Removed HCPCS NOC C9399 and J9999 and pending diagnosis codes for Vyloy; added HCPCS C9303 effective 2025-04-01 and ICD-10-CM codes C15.3–C15.9, C16.0–C16.9, Z85.01, Z85.028.

2024-11-22select review

Implemented new prior authorization for Vyloy (zolbetuximab-clzb); coding reviewed with addition of HCPCS NOC C9399 and J9999 and diagnosis placeholders.

C15.3-C15.9	Malignant neoplasm of esophagus
C16.0-C16.9	Malignant neoplasm of stomach
Z85.01	Personal history of malignant neoplasm of esophagus
Z85.028	Personal history of other malignant neoplasm of stomach

OpenPayer

Vyloy (zolbetuximab-clzb) — Coverage Criteria

Coverage Criteria for Vyloy (zolbetuximab-clzb)

Coding

Provider Actions and Administrative Requirements

Biomarker and Testing Requirements

Line of Therapy

Definitions

Background

Revision History