FDA approves zanidatamab for HER2-positive biliary tract cancer, including cholangiocarcinoma

Evidence stage: Later-Stage HumanRegulatory status: FDA-approved for the exact stated cancer/useGuideline status: Not addressed

The FDA granted accelerated approval to zanidatamab-hrii (Ziihera), a bispecific HER2-directed antibody, for adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer — a group of rare, aggressive cancers that includes cholangiocarcinoma (bile duct cancer) and gallbladder cancer. The approval was based on cohort 1 of the multicenter, single-arm, phase 2b HERIZON-BTC-01 trial (ClinicalTrials.gov NCT04466891; primary publication in The Lancet Oncology, DOI 10.1016/S1470-2045(23)00242-5, PMID 37276871), which enrolled 62 patients with HER2-positive biliary tract cancer who had already received gemcitabine-containing chemotherapy — the trial population was 53% gallbladder cancer, 27% intrahepatic cholangiocarcinoma, and 19% extrahepatic cholangiocarcinoma. Zanidatamab produced a confirmed objective response rate of 41.3% (52% per independent central review, the basis cited for the FDA’s approval decision) with a median duration of response of 14.9 months.

What This Means

In cohort 1 of the single-arm, phase 2b HERIZON-BTC-01 trial, zanidatamab -- a bispecific antibody that binds two separate sites on the HER2 protein -- produced a confirmed objective response in 41.3% of patients with previously treated, HER2-positive biliary tract cancer (a rare, aggressive group of cancers that includes cholangiocarcinoma and gallbladder cancer), with a median duration of response of 14.9 months, supporting FDA accelerated approval.

What This Doesn't Mean

This is a single-arm trial with no randomized comparison group, the basis for an ACCELERATED approval, not yet full/traditional approval -- continued approval may depend on results from a confirmatory trial. This record reports two response-rate figures rather than only the more favorable one: 41.3% by the trial's own primary analysis, and 52% by the independent central review the FDA's approval decision is reported to have cited -- readers should not assume these numbers are interchangeable without knowing which analysis a given source is citing.

Why It Matters

Biliary tract cancers are rare and historically have very limited treatment options once first-line chemotherapy fails; a targeted, biomarker-selected therapy with a real, durable response rate represents a genuine advance for a patient population this site had zero prior coverage of.

Promise & Proof

Proof — strength of the evidence 5 / 5
  • Base score from evidence stage: Later-Stage Human.
  • FDA-approved for the exact stated cancer/use.
Promise — potential significance if later evidence holds up 3 / 5
  • Baseline — a validly-evidenced story starts here; every further point below is an explicit, checkable reason.
  • The record includes substantive editorial reasoning about why this discovery matters.
  • A distinct follow-on/confirmatory study or trial is already cited as a secondary source — the field is already building on this finding.

These two ratings are automatically computed from this story's own structured evidence fields and are shown separately on purpose — they are never combined into one score. They describe this record, not a medical recommendation: they do not establish medical certainty, do not substitute for reading the cited sources, and are recalculated whenever the underlying evidence changes.

Population / Applicability

Studied in: Adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+ by central assessment) biliary tract cancer -- including cholangiocarcinoma and gallbladder cancer -- who had received prior gemcitabine-containing chemotherapy, enrolled in cohort 1 of the multicenter, single-arm, phase 2b HERIZON-BTC-01 trial. (Adults)

Requires HER2 (IHC 3+) testing by an FDA-approved companion diagnostic -- not appropriate for HER2-negative or lower-HER2-expression biliary tract cancer. This record has not independently reviewed the full safety/tolerability profile (known risks of HER2-directed antibodies include cardiac effects), which should be added before publication.

Full evidence details
Study design
Non-randomized trial
Sample size
62

Funding & Conflicts

Sponsor/developer: Jazz Pharmaceuticals (zanidatamab was originally developed by Zymeworks) -- not independently confirmed against a primary corporate-disclosure document.

Regulatory status by jurisdiction

United States (FDA)

Status
FDA-approved for the exact stated cancer/use
Indication
Adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by an FDA-approved test.
Biomarker requirement
HER2-positive (IHC 3+) by an FDA-approved companion diagnostic
Decision date
2024-11-20
Source
Regulator record (opens in a new tab)

Guideline positions

Guideline

Position
Not addressed
Last verified
2026-08-13

Primary evidence supporting this story

Additional context

Why Should I Trust This?

  • 1 source at Tier 2 — Peer-reviewed primary research, trial registries, regulatory documents, official conference abstracts
  • Last reviewed: 2026-08-13

This panel summarizes real, checkable facts about this record's own sources and review status — it is not a trust score, and reading it is not a substitute for reading the cited sources yourself.

Discovery Timeline

Every recorded change to this record's content or publication status, in order.

  1. Status change — Status changed from "Legacy / Unverified" to "In editorial review".
  2. Status change — Status changed from "In editorial review" to "Verified".

Last reviewed

Related discoveries

FDA approves zanidatamab for HER2-positive biliary tract cancer, including cholangiocarcinoma

https://cancerdiscoveries.com/discoveries/fda-approves-zanidatamab-for-her2-positive-biliary-tract-cancer-including-cholangiocarcinoma/

Evidence stage: Later-Stage Human

What This Means

In cohort 1 of the single-arm, phase 2b HERIZON-BTC-01 trial, zanidatamab -- a bispecific antibody that binds two separate sites on the HER2 protein -- produced a confirmed objective response in 41.3% of patients with previously treated, HER2-positive biliary tract cancer (a rare, aggressive group of cancers that includes cholangiocarcinoma and gallbladder cancer), with a median duration of response of 14.9 months, supporting FDA accelerated approval.

What This Doesn't Mean

This is a single-arm trial with no randomized comparison group, the basis for an ACCELERATED approval, not yet full/traditional approval -- continued approval may depend on results from a confirmatory trial. This record reports two response-rate figures rather than only the more favorable one: 41.3% by the trial's own primary analysis, and 52% by the independent central review the FDA's approval decision is reported to have cited -- readers should not assume these numbers are interchangeable without knowing which analysis a given source is citing.

Why It Matters

Biliary tract cancers are rare and historically have very limited treatment options once first-line chemotherapy fails; a targeted, biomarker-selected therapy with a real, durable response rate represents a genuine advance for a patient population this site had zero prior coverage of.

Primary sources

  • Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study (The Lancet Oncology) — https://doi.org/10.1016/S1470-2045(23)00242-5 (DOI 10.1016/S1470-2045(23)00242-5, PMID 37276871)

Date verified: 2026-08-13

Correction status: No correction or retraction