ModifiedmhnPolicy CP.PHAR.709

Zanidatamab-hrii (Ziihera)

Clinical coverage policy for zanidatamab‑hrii (Ziihera) addressing medical necessity, eligibility, dosing, and prior authorization expectations for adults with HER2‑positive biliary tract cancer across Centene lines of business.

Policy Summary

Payermhn

PolicyZanidatamab-hrii (Ziihera) for HER2-positive biliary tract cancer

Policy CodePolicy CP.PHAR.709

Change TypeCoding addition (HCPCS J9276)

Effective DateMar 1, 2025

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, HER2 IHC 3+, prior systemic therapy failure, oncologist involvement, age ≥18, and dosing within specified limits.

SourceLink

POLICY UPDATE CHANGES

HCPCS J9276 (injection, zanidatamab‑hrii, 2 mg) is referenced and added to coding.

IHC 3+HER2 test requirement for covered BTC patients

≥1Prior systemic therapy required (lines failed)

20 mg/kg q2wMaximum/approved dosing regimen for BTC

6 moInitial approval length

Embryo‑fetalSafety boxed warning

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Coverage Criteria

Initial Approval — Biliary Tract Cancer

Covered when ALL of the following are met for Initial Approval (Biliary Tract Cancer):

BTC Initial Approval: 1. Diagnosis of biliary tract cancer; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease is HER2‑positive (IHC 3+); 5. Disease is unresectable, resected gross residual (R2), or metastatic; 6. Failure of at least one prior systemic treatment (see Appendix B for examples); 7. Prescribed as a single agent; 8. Request meets one of the following: (a) dose does not exceed 20 mg/kg every 2 weeks; OR (b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: 6 months

Continuation Approval — Biliary Tract Cancer

Covered when ALL of the following are met for Continuation/Renewal (Biliary Tract Cancer):

BTC Continuation Approval: 1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Ziihera for a covered indication and has received this medication for at least 30 days; 2. Member is responding positively to therapy; 3. Prescribed as a single agent; 4. Dose requested is ≥ 15 mg/kg; 5. If request is for a dose increase, request meets one of the following: (a) new dose does not exceed 20 mg/kg every 2 weeks; OR (b) new dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM 12 months; Commercial 6 months or to renewal date, whichever is longer

Non‑FDA approved indications that are not specifically addressed in this policy are excluded from coverage unless the provider supplies sufficient documentation of efficacy and safety consistent with applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or unless coverage is otherwise supported by evidence of coverage documents.

This clinical policy and all materials contained herein are proprietary to Centene Corporation. Unauthorized copying, use, modification, distribution, or publication of this document or its contents is strictly prohibited without prior written permission from Centene Corporation. Do not alter or remove any trademark, copyright, or other notice contained in this publication.

Requests for coverage for diagnoses or indications not listed in this policy and lacking supporting evidence per the applicable off‑label use policies are considered not authorized for coverage.

Regimen	Indication	Status
Zanidatamab‑hrii 20 mg/kg IV every 2 weeks as single agent (until progression or unacceptable toxicity)
Previously treated unresectable or metastatic HER2‑positive (IHC 3+) biliary tract cancer
Covered when criteria met (see Initial Approval and Continuation sections)

Coding

Referenced HCPCS CodesHCPCS

J9276

Injection, zanidatamab-hrii, 2 mg

inv-07: Maximum Dose — 20 mg/kg every 2 weeks.

Maximum dose20 mg/kg every 2 weeks

Administration routeIntravenous (IV)

Use duration guidanceUntil disease progression or unacceptable toxicity

Context of regimenApproved dosing for biliary tract cancer (BTC)

inv-08: Minimum dose for continuation requests — ≥ 15 mg/kg.

Minimum dose for continuation requests≥ 15 mg/kg

Tolerance note

Provider Actions & Administrative Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must include documentation of diagnosis (biliary tract cancer), HER2 testing showing IHC 3+, prior systemic therapy failure per the criteria (see Appendix B), prescriber involvement (oncologist or consultation), age (≥18 years), and dosing that meets the policy (≤20 mg/kg every 2 weeks or literature/guideline support for off‑label dose). Prescribers must submit supporting evidence when dosing exceeds the labeled regimen.

Prior authorization required before initiation
Include oncologist involvement/consultation
Include HER2 IHC 3+ test results
Document failure of ≥1 prior systemic therapy (see Appendix B)
If dose exceeds 20 mg/kg Q2W, submit guideline or peer‑reviewed literature supporting the dose

Documentation Required

Supporting Documentation

Line of Therapy

Second‑line

Previously treated BTC: Requirement: Failure of at least one prior systemic treatment (i.e., used in previously treated setting).

Biomarker Requirements

inv-22: HER2 (IHC) — A HER2 immunohistochemistry test score indicating high HER2 protein overexpression (score ranges 0–3+; 3+ required for efficacy population).

DefinitionA HER2 immunohistochemistry (IHC) test score indicating high HER2 protein overexpression; scores range 0–3+

Required threshold for efficacy populationIHC 3+ (HER2 IHC 3+ required)

Clinical contextEfficacy of Ziihera in BTC was established in patients with HER2 IHC 3+ (HERIZON-BTC-302 trial)

Definitions & Notices

inv-18: HER2 IHC 3+ — definition of required biomarker threshold.

Biomarker thresholdHER2 IHC 3+

Score range0 to 3+

Evidence noteEfficacy established in 62 patients with HER2-positive (IHC 3+) BTC in HERIZON-BTC-302 trial

inv-19: Provider status — Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan does not exercise control.

Provider statusProviders are independent contractors who exercise independent judgment and are not agents or employees of the Health Plan.

Control relationshipThe Health Plan has no control or right of control over providers referenced in this policy.

Background

Zanidatamab‑hrii (Ziihera) is a bispecific HER2‑directed antibody that received accelerated approval for use in adults with previously treated, unresectable or metastatic HER2‑positive biliary tract cancer (HER2 IHC 3+). Approval was granted based on overall response rate and duration of response; confirmatory trials may be required to verify clinical benefit.

Policy Summary

Payermhn

PolicyZanidatamab-hrii (Ziihera) for HER2-positive biliary tract cancer

Policy CodePolicy CP.PHAR.709

Change TypeCoding addition (HCPCS J9276)

Effective DateMar 1, 2025

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, HER2 IHC 3+, prior systemic therapy failure, oncologist involvement, age ≥18, and dosing within specified limits.

SourceLink

On This Page

Ziihera should be permanently discontinued in patients who cannot tolerate 15 mg/kg per product labeling.

Continuation requirementMember must have received ≥30 days of therapy and be responding to treatment

Provider must submit supporting documentation (e.g., office chart notes, HER2 laboratory results, prior therapy records, imaging, and any other clinical information) demonstrating the member meets all approval criteria. Incomplete documentation may result in denial.

Chart notes and relevant lab/pathology reports (HER2 IHC)
Records of prior systemic therapies and outcomes
Documentation of oncologist involvement/consultation

Note

Therapeutic Alternatives

Therapeutic alternatives should be considered per Appendix B. Examples of systemic regimens include gemcitabine + cisplatin (± immunotherapy), FOLFOX, capecitabine + oxaliplatin, single‑agent 5‑FU, capecitabine, or gemcitabine, and other combinations listed in Appendix B. These agents may require prior authorization and formulary considerations.

Examples: Imfinzi® + gemcitabine + cisplatin; Keytruda® + gemcitabine + cisplatin; gemcitabine + cisplatin/oxaliplatin; FOLFOX; capecitabine + oxaliplatin; single agents (5‑FU, capecitabine, gemcitabine)
See Appendix B for full list and dosing considerations

Denial Risk

Non‑FDA Indications — Risk of Denial

Requests for non‑FDA‑approved (off‑label) indications not addressed in this policy may be denied unless sufficient documentation of efficacy and safety is provided consistent with the plan's off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents. When an off‑label dose or indication is requested, prescriber must submit supporting peer‑reviewed literature or guideline recommendations.

Off‑label uses must reference supporting evidence per applicable off‑label policy
Failure to provide sufficient evidence may result in denial

Note

Provider Contractual Obligations

Providers are bound to the terms and conditions expressed in this clinical policy through their contractual relationship with the Health Plan. Where no contract exists, providers, members, and their representatives agree to be bound by these terms by providing services to members and/or submitting claims for payment. The policy is proprietary and unauthorized copying or distribution is prohibited.

Providers are independent contractors; not agents or employees of the Health Plan
Submitting claims for payment or providing services indicates agreement to the policy terms

Note

Medicaid Precedence

For Medicaid members, state Medicaid coverage provisions take precedence if they conflict with this clinical policy. Refer to the applicable state Medicaid manual for any differing coverage rules or procedures.

State Medicaid provisions supersede this policy when in conflict
Consult the state Medicaid manual for specific coverage details

Contractual bindingProviders are bound to the policy terms and conditions through contract or by providing services/submitting claims.

inv-20: Proprietary notice — This clinical policy is proprietary material owned by Centene Corporation with reproduction and distribution restrictions.

OwnershipThis clinical policy is proprietary material owned exclusively by Centene Corporation.

RestrictionsNo part may be reproduced, copied, modified, distributed, displayed, stored, transmitted, or published without prior written permission of Centene Corporation; trademarks must not be altered or removed.