CurrentmhnPolicy CP.PHAR.750

Zongertinib (Hernexeos) — Coverage Criteria for HER2-mutant NSCLC

Defines medical necessity and prior authorization criteria for zongertinib (Hernexeos) for adult patients with unresectable or metastatic nonsquamous NSCLC harboring activating HER2 (ERBB2) mutations; applies to members under Centene-affiliated health plans including commercial, HIM, and Medicaid.

Policy Summary

Payermhn

PolicyZongertinib (Hernexeos) — Coverage Criteria for HER2-mutant NSCLC

Policy CodePolicy CP.PHAR.750

Change TypeNo material changes

Effective DateAug 18, 2025

Next Review Date

Key ActionSubmit prior authorization with documentation proving unresectable/metastatic nonsquamous NSCLC with activating HER2 mutation and prior systemic therapy failure.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthsstandard approval duration

60 mgtablet strength available

120/180 mgFDA dosing regimens

Adultage requirement

HER2-mutant NSCLCindication scope

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Coverage Criteria

inv-01: Initial Therapy

Covered when ALL of the following are met

Initial Approval for NSCLC

Diagnosis of unresectable, recurrent, advanced, or metastatic NSCLC
Prescriber: Prescribed by or in consultation with an oncologist
Age ≥ 18 years
Single agent: Prescribed as single agent
Molecular marker: Disease has activating HER2 (ERBB2) mutations
Prior therapy: Failure of a prior systemic therapy (see Appendix B for examples)
Product preference: Member must use zongertinib if available unless contraindicated or clinically significant adverse effects are experienced
Dose requirement
- Weight-based dosing: Dose does not exceed: for body weight < 90 kg: 120 mg per day (2 tablets); for body weight ≥ 90 kg: 180 mg per day (3 tablets)120 mg or 180 mg per day
- Off-label dose support: Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence)

Non-FDA approved indications that are not specifically addressed in this policy are excluded from coverage unless the provider submits sufficient documentation of efficacy and safety consistent with the referenced off‑label use policies (see CP.CPA.09, HIM.PA.154, and CP.PMN.53).

Uses for indications that are not FDA‑approved and are not supported under the referenced off‑label use policies are considered not authorized (not covered). Providers must follow the procedures and evidentiary standards in CP.CPA.09 (Commercial), HIM.PA.154 (HIM), or CP.PMN.53 (Medicaid) when requesting coverage for off‑label uses.

Coding and Dosing

Indication / descriptivemixed

N/A

No procedure or diagnosis codes explicitly listed in the policy document; indication described in plain language: unresectable or metastatic nonsquamous non-small cell lung cancer (NSCLC) with HER2 (ERBB2) tyrosine kinase domain activating mutations in adults who have received prior systemic therapy

inv-07: Maximum daily dose

Maximum daily dose180 mg/day

Source contextPolicy lists maximum dose under Dosage and Administration as 180 mg/day

Approval noteDose limits referenced in Initial Approval Criteria and Dosage and Administration sections

inv-08: Weight-based dosing thresholds

Body weight < 90 kg120 mg/day (2 tablets)

Policy sourceWeight-based dosing specified in Initial Approval Criteria and Dosage and Administration

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization required. Requests must demonstrate the member meets the plan’s clinical criteria for unresectable, recurrent, advanced, or metastatic nonsquamous non–small cell lung cancer (NSCLC) with activating HER2 (ERBB2) mutations and all other criteria in the policy (e.g., age ≥ 18, prescribed by or in consultation with an oncologist, single-agent use, prior systemic therapy failure, dosing limits or literature support, and use of zongertinib if available unless contraindicated). Approval duration is 12 months for initial and continued therapy when criteria are met.

Initial and continued therapy criteria located in policy sections I and II
Dose limits: <90 kg = 120 mg/day (2 tablets); ≥90 kg = 180 mg/day (3 tablets) unless supported by guidelines/literature
Member must have failed prior systemic therapy (see Appendix B for examples)
Prescribed regimen must be FDA‑approved or recommended by NCCN

Denial Risk

Background

Zongertinib (Hernexeos) is a kinase inhibitor approved under accelerated approval for adult patients with unresectable or metastatic nonsquamous non‑small cell lung cancer harboring activating HER2 (ERBB2) tyrosine kinase domain mutations after prior systemic therapy; continued approval depends on verification of clinical benefit. Requests for uses outside the FDA‑approved indication must meet the documentation requirements described in the off‑label use policies referenced above.

Definitions

inv-14: NSCLC

DefinitionNon-small cell lung cancer (NSCLC)

ContextIndication described as unresectable or metastatic nonsquamous NSCLC in FDA-approved indication

AbbreviationNSCLC = non-small cell lung cancer

inv-15: HER2 (ERBB2) activating mutation

Mutation describedHER2 (ERBB2) tyrosine kinase domain activating mutations

Detection requirementDetected by an FDA-approved test per FDA-approved indication

Indication linkageRequired for use in unresectable or metastatic nonsquamous NSCLC per policy and FDA label

Initial Therapy Criteria

Continuation Criteria

Step Therapy / Therapeutic Alternatives

Step	Therapeutic alternatives / notes
1	Therapeutic alternatives are listed in Appendix B and may be considered prior to approval per formulary/PDL status. Appendix B lists preferred alternative regimens (examples include platinum-based chemotherapy with pembrolizumab, cemiplimab-rwlc combinations, atezolizumab-containing regimens, and nivolumab/ipilimumab regimens); these alternatives may require prior authorization where applicable.

Quantity Limits

inv-19: Zongertinib (Hernexeos)

Product name and brandZongertinib (Hernexeos)

Maximum daily doseMax 180 mg/day

Tablet strength60 mg tablet available

Site of Care

Note

No site‑of‑care restrictions specified

No site‑of‑care restrictions are specified in this policy; the policy lists the setting as office with no limitations on site of care.