CurrentEmblemHealthPolicy MG.MM.PH.418

Vyloy (zolbetuximab-clzb) — coverage criteria for CLDN18.2‑positive gastric/GEJ adenocarcinoma

Covers clinical criteria, dosing, coding, and authorization rules for Vyloy (zolbetuximab-clzb) used with fluoropyrimidine- and platinum-based chemotherapy as first-line therapy for adults with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma.

Policy Summary

PayerEmblemHealth

PolicyVyloy (zolbetuximab-clzb) — coverage criteria for CLDN18.2‑positive gastric/GEJ adenocarcinoma

Policy CodePolicy MG.MM.PH.418

Change TypeNew policy

Effective Date

Next Review DateDec 12, 2024

Key ActionSubmit clinical documentation demonstrating age, histology, CLDN18.2 IHC ≥75%, HER2-negative status, and planned concomitant fluoropyrimidine- and platinum-containing chemotherapy when requesting prior authorization.

SourceLink

POLICY UPDATE CHANGES

New policy for Vyloy (zolbetuximab-clzb) was created.

6 monthsinitial length of authorization

2000 mgfirst-dose maximum

1500 mg q3w / 1000 mg q2wsubsequent dosing

CLDN18.2 ≥75%IHC positivity

≥18

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Coverage Criteria for Vyloy (zolbetuximab-clzb)

Initial Criteria (First-line therapy)

Covered when ALL of the following are met

Universal eligibility: 1. Patient is at least 18 years of age; AND 2. Patient is not experiencing Grade 2 or greater nausea and/or vomiting prior to the first infusion; AND 3. Patient does not have a complete or partial gastric outlet syndrome; AND 4. Patient does not have a history of central nervous system metastases;

Universal criteria required before indication-specific criteria

Indication-specific criteria for gastric/GEJ adenocarcinoma: a. Patient has locally advanced unresectable, or metastatic adenocarcinoma; AND b. Used as first-line therapy; AND c. Patient has claudin (CLDN) 18.2–positive disease (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18.2 immunohistochemical staining) determined by an FDA-approved or CLIA-compliant test; AND d. Patient has HER2-negative disease; AND e. Used in combination with a fluoropyrimidine- and platinum-containing chemotherapy-based regimen

All indication-specific items required

Renewal Criteria

Renewal (continuation) criteria — coverage may be renewed when ALL of the following are met

Renewal requirements: 1. Patient continues to meet the universal and indication-specific relevant criteria (including concomitant therapy requirements); AND 2. Disease response with treatment defined by stabilization of disease or decrease in size of tumor or tumor spread; AND 3. Absence of unacceptable toxicity from the drug (examples include severe hypersensitivity reactions including anaphylaxis, severe nausea and vomiting).

Clinical response and tolerability required for renewal

The following clinical conditions exclude patients from initial coverage: Grade 2 or greater nausea and/or vomiting prior to the first infusion, a complete or partial gastric outlet syndrome, or a history of central nervous system metastases. These exclusions are required to be absent before initiating therapy.

Use of Vyloy outside the specified patient population is not supported. The policy is limited to first-line use only and requires tumors to be HER2-negative and CLDN18.2-positive (see biomarker definition). Pediatric patients <18 years of age are not eligible under these criteria.

Regimen	Indication	Line of therapy	Coverage status
Vyloy (zolbetuximab-clzb) in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen	First-line treatment of CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma	First-line	Covered when initial criteria are met

Applicable Codes and Biomarker Definitions

Applicable Procedure CodesHCPCS

J9999	Not otherwise classified, antineoplastic drugs.
C9399	Unclassified drugs or biologicals (hospital outpatient use)

Applicable NDCsNDC

00469-3425-xx

Vyloy 100 mg powder in a single-dose vial

Applicable ICD-10 DiagnosesICD-10

C15.3	Malignant neoplasm of upper third of esophagus.
C15.4	Malignant neoplasm of middle third of esophagus.
C15.5	Malignant neoplasm of lower third of esophagus.
C15.8	Malignant neoplasm of overlapping sites of esophagus
C15.9	Malignant neoplasm of esophagus, unspecified.
C16.0	Malignant neoplasm of cardia.
C16.1	Malignant neoplasm of fundus of stomach.
C16.2	Malignant neoplasm of body of stomach.
C16.3	Malignant neoplasm of pyloric antrum.
C16.4	Malignant neoplasm of pylorus.

1–10 of 20

1/2

CLDN18.2 IHC positivity — threshold

DefinitionCLDN18.2 IHC positivity is defined as ≥75% of tumor cells demonstrating moderate to strong membranous staining.

Assessment methodDetermined by immunohistochemistry (IHC) on tumor tissue.

Clinical contextRequired to identify patients eligible for Vyloy in combination with fluoropyrimidine- and platinum-containing chemotherapy.

Biomarker and Test Requirements

CLDN18.2 testing requirements

Positivity thresholdCLDN18.2-positive defined as ≥75% of tumor cells with moderate to strong membranous IHC staining.

Test requirementsMust be determined by an FDA-approved or CLIA-compliant test.

Indication linkRequired for first-line Vyloy use in locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.

HER2 requirement

RequirementTumor must be HER2-negative to meet eligibility for Vyloy therapy.

Clinical significanceHER2-negative status is part of the indication for first-line Vyloy with chemotherapy in gastric/GEJ adenocarcinoma.

Line-of-Therapy Requirement

Documentation Required

Prior Authorization Documentation

Provider must submit documentation supporting diagnosis and line-of-therapy. Documentation required includes: clinic notes, pathology/immunohistochemistry report showing CLDN 18.2 positivity (≥75% tumor cells with moderate–strong membranous staining) from an FDA-approved or CLIA-compliant test, HER2 testing results, and chemotherapy regimen details showing use in combination with a fluoropyrimidine- and platinum-containing regimen.

Include pathology/IHC report confirming CLDN 18.2 positive status (≥75% tumor cells with moderate–strong membranous staining) from an FDA-approved or CLIA-compliant test.
Provide HER2-negative test results.
Submit clinical notes confirming diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
Provide treatment plan or infusion records showing Vyloy will be used in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen.
Age verification (patient ≥18 years) and assessment notes ruling out Grade ≥2 nausea/vomiting, gastric outlet obstruction, and CNS metastases.

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior authorization required; 6-month authorization and dosing limits

Prior authorization is required for Vyloy and coverage is provided when initial criteria are met. The initial authorization duration is 6 months and may be renewed. Dosing limits are: first dose 2000 mg (one time only); subsequent doses 1500 mg every 3 weeks or 1000 mg every 2 weeks.

HCPCS codes: J9999, C9399 (per policy coding group).

Documentation Required

Submit documentation of eligibility (age, histology, biomarkers, planned regimen)

Provider must submit clinical evidence that the member meets all coverage criteria, including age (≥18 years), performance/clinical status and specified exclusions, histology (locally advanced unresectable or metastatic adenocarcinoma), CLDN18.2 testing results (IHC ≥75% moderate to strong membranous staining by an FDA‑approved or CLIA‑compliant test), HER2‑negative status, and the plan to use Vyloy in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen.

Covered Chemotherapy Regimens with Vyloy

Detail	Requirement / Value
Patient age	At least 18 years
Exclusion criteria (examples)	Grade ≥2 nausea/vomiting prior to first infusion; complete or partial gastric outlet syndrome; history of CNS metastases
Biomarker requirement	CLDN18.2-positive defined as ≥75% of tumor cells with moderate to strong membranous IHC staining determined by an FDA‑approved or CLIA‑compliant test
HER2 status	HER2-negative
Concomitant therapy	Must be used in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen
Authorization	Prior authorization required; initial authorization duration 6 months; may be renewed if renewal criteria met
Dosing limits	First dose maximum one-time: 2000 mg (20 vials); Subsequent doses: 1500 mg every 3 weeks or 1000 mg every 2 weeks
Documentation required	Submit clinical evidence of age, histology (locally advanced unresectable or metastatic adenocarcinoma), CLDN18.2 IHC result, HER2-negative status, planned concomitant fluoropyrimidine- and platinum-containing chemotherapy, and clinical status

Background

Vyloy (zolbetuximab-clzb) is indicated, per this policy, in combination with a fluoropyrimidine- and platinum-containing chemotherapy regimen for the first-line treatment of adults with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors are CLDN18.2-positive and HER2-negative. Eligible patients must be at least 18 years of age and meet the listed universal criteria (no significant pre-infusion nausea/vomiting, no gastric outlet syndrome, and no history of CNS metastases) prior to initiation.

Revision History

2024-12-12Policy createdLatest

New policy for Vyloy (zolbetuximab-clzb) was created and entered into EmblemHealth’s policy library.