CurrentCignaPolicy N/A

Oncology (Oral - HER2 Inhibitor) - Hernexeos Prior Authorization Policy

Cigna prior authorization policy for oral HER2 inhibitor Hernexeos (zongertinib) covering use in adults with unresectable or metastatic non‑small cell lung cancer harboring ERBB2 (HER2) activating mutations; applies to prescription benefit plans administered by Cigna companies.

Policy Summary

PayerCigna

PolicyOncology (Oral - HER2 Inhibitor) - Hernexeos Prior Authorization Policy

Policy CodePolicy N/A

Change TypeContent updates and editorial revision (08/21/2025; 09/10/2025)

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of age, metastatic/unresectable disease, ERBB2 (HER2) activating mutation by an FDA‑approved test, and prior systemic therapy.

SourceLink

POLICY UPDATE CHANGES

Overview updated with new guideline information.

Deleted 'nonsquamous' in reference to disease type for Non‑Small Cell Lung Cancer.

1 yeartypical approval duration

≥18minimum patient age for coverage

prior therapyline of therapy requirement

NCCN 2Aguideline recommendation

Recommended Authorization Criteria

Initial Authorization — Non‑Small Cell Lung Cancer

Covered when ALL of the following are met:

FDA‑Approved Indication (NSCLC): A) Patient is ≥ 18 years of age; AND B) Patient has unresectable or metastatic disease; AND C) Patient has human epidermal growth factor receptor 2 (HER2) [ERBB2] activating mutation; AND D) The mutation was detected by an approved test; AND E) Patient has received at least one prior systemic therapy.

Approve for 1 year.

Use of Hernexeos® (zongertinib) for indications or circumstances not explicitly listed in the Recommended Authorization Criteria is not medically necessary and is not recommended for coverage. Review of requests should confirm the treatment indication aligns with the criteria set forth in this policy; requests that fall outside those criteria may be denied.

Hernexeos® (zongertinib) is considered not medically necessary for any uses other than the specified FDA‑approved indication(s). This policy’s criteria will be updated as new published data become available; providers should check the policy for the most recent updates before submitting requests.

Approval Duration & Codes

Covered CPT/HCPCS/ICD-10 codesmixed

No codes listed

Approval duration

Typical approval duration1 year

Approval applies when all FDA‑approved indication criteria are metApprove for 1 year if patient meets criteria A–E (age ≥18, unresectable/metastatic disease, ERBB2 activating mutation, mutation detected by an approved test, prior systemic therapy)

Duration reference in policy'Approve for 1 year' stated in FDA‑Approved Indication section

Prior Authorization & Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for prescription benefit coverage of Hernexeos. Approvals are provided for the duration noted in the FDA‑Approved Indication (1 year).

Prior authorization required — approve for 1 year when criteria met
Submit request before dispensing to avoid denial

Step Therapy

Prior Therapy Requirement

Patient must have received at least one prior systemic therapy before starting Hernexeos. NCCN guidelines list HER2‑directed ADCs (Enhertu, Kadcyla) and Hernexeos as subsequent therapy options for ERBB2 (HER2) mutation‑positive NSCLC; ensure prior therapy history is documented.

Document prior systemic therapy (examples: checkpoint inhibitor +/- chemotherapy, platinum doublet, docetaxel, gemcitabine)

Recommended Regimens and Guideline Placement

Regimen	NCCN placement / category	Notes
Hernexeos (zongertinib)	Preferred subsequent therapy (Category 2A)	Listed as a preferred subsequent HER2-directed therapy for ERBB2 (HER2) mutation–positive NSCLC; may be used upon subsequent therapy progression if not previously received.
Enhertu (fam-trastuzumab deruxtecan-nxki)	Preferred subsequent therapy (Category 2A)	Included with Hernexeos as preferred subsequent HER2-directed therapy (antibody–drug conjugate; intravenous).
Kadcyla (ado-trastuzumab emtansine)	Other recommended subsequent therapy (Category 2A)	Recommended as an 'Other Recommended' subsequent therapy option; can be used if not received previously or upon progression.

Line of Therapy Requirements

second-line | subsequent

Line of therapy: Patient has received at least one prior systemic therapy (i.e., subsequent therapy setting).

NCCN lists Hernexeos as a preferred subsequent therapy (category 2A).

Genetic Testing and Biomarker Confirmation

ERBB2 (HER2) — testing requirement

Required test typeThe ERBB2 (HER2) activating mutation must be detected by an FDA‑approved test

Policy basisIndication specifies tumors with ERBB2 tyrosine kinase domain activating mutations 'as detected by an FDA‑approved test'

Testing expectation in coverage criteriaFDA‑Approved Indication requires the mutation was detected by an approved test (criterion D)

Key Definitions

HER2 (ERBB2) activating mutation — definition

DefinitionERBB2 (HER2) activating mutation: a pathogenic alteration in the ERBB2 tyrosine kinase domain conferring eligibility for HER2‑directed therapy

Detection expectationMutation must be identified by an FDA‑approved/cleared test to meet coverage criteria

Clinical contextHernexeos is indicated for unresectable or metastatic NSCLC with ERBB2 tyrosine kinase domain activating mutations in adults who have received prior systemic therapy

Background

Hernexeos (zongertinib) is an oral kinase inhibitor indicated for the treatment of adults with unresectable or metastatic non‑small cell lung cancer (NSCLC) harboring activating ERBB2 (HER2) tyrosine kinase domain mutations who have received prior systemic therapy. The National Comprehensive Cancer Network (NCCN) lists Hernexeos among preferred subsequent HER2‑directed therapies (category 2A) for ERBB2‑mutant NSCLC. When the FDA‑approved criteria are met, approvals are provided for 1 year.

Policy Summary

PayerCigna

PolicyOncology (Oral - HER2 Inhibitor) - Hernexeos Prior Authorization Policy

Policy CodePolicy N/A

Change TypeContent updates and editorial revision (08/21/2025; 09/10/2025)

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization with documentation of age, metastatic/unresectable disease, ERBB2 (HER2) activating mutation by an FDA‑approved test, and prior systemic therapy.

SourceLink

On This Page

If prior therapy includes a HER2‑directed agent, note sequence and response

Documentation Required

Required Documentation

Providers must submit documentation to support medical necessity with the prior authorization request. Required documentation includes: patient age, diagnosis of unresectable or metastatic NSCLC, evidence of an activating ERBB2 (HER2) mutation and the test report showing the mutation was detected (approved test), detailed systemic therapy history (at least one prior regimen with dates and response), and any relevant clinical notes (stage, performance status, prior HER2‑directed therapies if given).

Patient age (≥ 18 years)
Diagnosis: unresectable or metastatic NSCLC
Genetic test result: ERBB2 (HER2) activating mutation — specify approved test and report
Prior systemic therapy: agents, dates, and response (must show at least one prior systemic therapy)
Clinical notes: disease stage, performance status, prior HER2‑targeted therapies and reason for discontinuation

Denial Risk

Denial Triggers / Non‑Covered Uses

Requests that do not meet the authorization criteria or that seek Hernexeos for any use not listed in the Recommended Authorization Criteria will be denied. Coverage is not recommended for circumstances not specified in the criteria; criteria will be updated as new published data are available.

Denial triggers: age < 18 years, no unresectable/metastatic disease, absence of ERBB2 activating mutation or missing mutation test report, no prior systemic therapy documented
Denial for non‑FDA uses or indications not supported by the stated criteria