HERIZON-BTC-01
A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers
Phase 2N = 87NCT04466891
- Population
- Adults with HER2-amplified (central in-situ hybridisation) unresectable, locally advanced or metastatic biliary tract cancer, progression on previous gemcitabine-based therapy, ECOG performance status 0 or 1 and at least one measurable lesion; 80 patients in cohort 1 (IHC 2+ or 3+) and seven in cohort 2 (IHC 0 or 1+).
- Design
- Global, multicentre, single-arm phase 2b trial at 32 sites in nine countries of zanidatamab 20 mg/kg intravenously every 2 weeks in HER2-amplified (in-situ hybridisation, central testing) unresectable, locally advanced or metastatic biliary tract cancer with progression on previous gemcitabine-based therapy. Cohort 1: HER2 immunohistochemistry (IHC) 2+ or 3+ (HER2-positive); cohort 2: IHC 0 or 1+. Primary endpoint: confirmed objective response rate in cohort 1 by independent central review. Median duration of follow-up 12.4 months (IQR 9.4-17.2); data cutoff 10 October 2022. Single-arm; no comparison group.
- Primary endpoint
- ORR
- Arms
- Zanidatamab (experimental, n = 87): Zanidatamab 20 mg/kg intravenously every 2 weeks
- People
- Harding JJ
Show the numbers
| Endpoint | Analysis | Zanidatamab | Control | Effect |
|---|---|---|---|---|
| ORRCohort 1: HER2-positive (IHC 2+ or 3+) (80)Confirmed objective response by independent central review | primaryHarding 2023 | 41.3% (30.4–52.8%) | — | 33 of 80 patients in cohort 1 had a confirmed response. The abstract does not give a median duration of response. |
| ORRCohort 1 patients with HER2-positive (IHC 3+ by central assessment) disease (62)Objective response rate by independent central review as printed in the FDA label | exploratorySource 2026 | 52% (39–65%) | — | Label table: three complete responses (4.8%) and 29 partial responses (47%). The label's clinical studies section gives no data cutoff, so these figures may reflect a later cutoff than the 2023 paper. This is the IHC 3+ subset of cohort 1 (the paper's primary analysis covers all 80 patients in cohort 1) and the population on which the FDA indication (IHC 3+) rests; the label names ORR and DOR as the major efficacy outcome measures in it. |
| DORResponders among the 62 IHC 3+ patients (32) | exploratorySource 2026 | median 14.9 months (7.4–24.0) | — | Kaplan-Meier estimate as printed in the label; 63% of responders had an observed response duration of at least 6 months and 44% at least 12 months. |
| Endpoint | Analysis | Zanidatamab | Control | Effect |
|---|---|---|---|---|
| ORRCohort 1: HER2-positive (IHC 2+ or 3+) (80)Confirmed objective response by independent central review | primaryHarding 2023 | 41.3% (30.4–52.8%) | — | 33 of 80 patients in cohort 1 had a confirmed response. The abstract does not give a median duration of response. |
| ORRCohort 1 patients with HER2-positive (IHC 3+ by central assessment) disease (62)Objective response rate by independent central review as printed in the FDA label | exploratorySource 2026 | 52% (39–65%) | — | Label table: three complete responses (4.8%) and 29 partial responses (47%). The label's clinical studies section gives no data cutoff, so these figures may reflect a later cutoff than the 2023 paper. This is the IHC 3+ subset of cohort 1 (the paper's primary analysis covers all 80 patients in cohort 1) and the population on which the FDA indication (IHC 3+) rests; the label names ORR and DOR as the major efficacy outcome measures in it. |
| DORResponders among the 62 IHC 3+ patients (32) | exploratorySource 2026 | median 14.9 months (7.4–24.0) | — | Kaplan-Meier estimate as printed in the label; 63% of responders had an observed response duration of at least 6 months and 44% at least 12 months. |
- Zanidatamab (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Zanidatamab |
|---|---|
| 0 | 100.0% |
| 9 | 65.8% |
| 19 | 41.3% |
| 28 | 27.2% |
| 37 | 17.9% |
Appears in
Sources
Harding JJ, Fan J, Oh DY, Choi HJ, Kim JW, Chang HM, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023;24(7):772-782.
FDA. Prescribing information, Ziihera (zanidatamab-hrii), label version effective 24 August 2026 (openFDA drug label record, set ID ae5d9425-fae5-4541-a158-150998343348).