VA Criteria for Use Formulary Advisor Reference
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ZANIDATAMAB-HRII INJ

Generic Name
ZANIDATAMAB-HRII INJ
Brand Names
ZIIHERA
Drug Class
ANTINEOPLASTIC,OTHER
Formulary Status
Non-Formulary Requires prior authorization
Copay Tier
3
Last Updated
March 1, 2026

Clinical Criteria Summary

Document 837: MON Zanidatamab hrii ZIIHERA Monograph Mar 2026

Indication & Patient Population

  • Adults with previously treated, unresectable or metastatic biliary tract cancer (BTC)
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Left ventricular ejection fraction ≥ 50%

Diagnostic & Disease State Requirements

  • HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test
  • Confirmed HER2-amplified, unresectable, locally advanced, or metastatic BTC (gallbladder cancer [GBC], intrahepatic cholangiocarcinoma [ICC], or extrahepatic cholangiocarcinoma [ECC])
  • Presence of ≥ 1 measurable target lesion

Prior Therapy & Treatment History

  • Disease progression on ≥ 1 gemcitabine-based systemic therapy for unresectable, locally advanced, or metastatic disease
  • Progression or recurrence within 6 months of completion in the neoadjuvant or adjuvant setting
  • No prior treatment with HER2-targeting agents

Dosing & Administration Parameters

  • 20 mg/kg by IV infusion once every 2 weeks
  • Continue therapy until disease progression or unacceptable toxicity

Safety & Monitoring Considerations

  • Boxed warning for embryofetal toxicity
  • Other warnings include left ventricular dysfunction, infusion-related reactions, and diarrhea
  • Discontinuation due to adverse events occurred in 2.5% of patients (Cohort 1)
  • Serious treatment-related adverse events occurred in 8% overall

Place in Therapy & Formulary Context

  • Subsequent-line therapy for BTC if disease progression
  • Category 2A recommendation for HER2+ by IHC3+ per NCCN guidelines
  • Indirect comparisons indicate no additional benefit over existing available therapies and a more inconvenient dosing schedule (every 2 weeks vs every 3 weeks)
  • May be considered for patients unable to receive fam-trastuzumab deruxtecan due to concern for interstitial lung disease (ILD), though trastuzumab + tucatinib or trastuzumab + pertuzumab may be preferred for improved objective response rate and more convenient dosing
  • Consider differences in study enrollment criteria when evaluating outcome comparisons across alternatives

Document 848: Zanidatamab ZIIHERA Criteria Mar 2026

Exclusion Criteria

  • Left Ventricular Ejection Fraction < 50%
  • Pregnancy
  • Lactating

Inclusion Criteria

  • Care provided by a VA or VA Community Care oncology provider
  • Eastern Cooperative Oncology Group Performance Status 0 - 2
  • Unresectable or metastatic biliary tract cancer
  • Progressive disease on at least one prior chemotherapy regimen
  • Patient is not a candidate for fam-trastuzumab deruxtecan, trastuzumab/tucatinib or trastuzumab/pertuzumab

Additional Inclusion Criteria

  • For females who can become pregnant: Pregnancy should be excluded prior to receiving zanidatamab
  • For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 months after stopping treatment

Source Documents

Document 837: MON Zanidatamab hrii ZIIHERA Monograph Mar 2026 Document 848: Zanidatamab ZIIHERA Criteria Mar 2026