Zanidatamab in HER2-Positive Metastatic Biliary Tract Cancer: Final Results From HERIZON-BTC-01
Mené sur 80 patients atteints d'un cancer des voies biliaires HER2+ de stade localement avancé ou métastatique (âge médian : 64 ans ; durée médiane de suivi : 33,4 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du zanidatamab (un anticorps bispécifique ciblant HER2)
Metastatic biliary tract cancer (BTC) has a poor prognosis (median overall survival [OS] <13 months with first-line therapies and 6-9 months for subsequent chemotherapy). Human epidermal growth factor receptor 2 (HER2; encoded by ERBB2) overexpression occurs in a subset of BTC and is a precision therapy target. Zanidatamab, a dual HER2-targeted bispecific antibody, received accelerated US approval for adults with previously treated, unresectable, or metastatic HER2-positive (immunohistochemistry [IHC] score of 3+) BTC and conditional authorization in the European Union and China based on the phase 2 HERIZON-BTC-01 trial.
Here, we report the final analysis of HERIZON-BTC-01, which includes OS and patient-reported outcome of worst pain in patients with ERBB2-amplified BTC with an IHC score of 3+ or 2+ after 33 months of follow-up.
Methods: In HERIZON-BTC-01 (NCT04466891), patients with ERBB2-amplified, locally advanced, or metastatic BTC with disease progression with or following prior gemcitabine-based therapy received zanidatamab, 20 mg/kg, intravenously every 2 weeks in 28-day cycles. Trial sites received local independent ethics committee approval. Participants provided written informed consent. The trial protocol is in Supplement 1 and the statistical analysis plan in Supplement 2. The primary end point was confirmed objective response rate (cORR) by independent central review. Secondary end points included duration of response, disease control rate, progression-free survival, OS, and safety outcomes. Patient-reported worst pain in the last 24 hours was evaluated using the Brief Pain Inventory-Short Form (rated 0 [no pain] to 10 [worst pain imaginable]). Analyses were conducted using SAS version 9.4.
Results: Between September 15, 2020, and March 16, 2022, 80 patients (45 [56%] female; 35 [44%] male; median [range] age, 64 [32-79] years) with IHC 2+ or 3+ tumors were enrolled. The median (range) follow-up was 33.4 (28.0-45.0) months, an additional 21 months from the initial report. Thirty-five patients (44%) received anticancer therapy after discontinuing zanidatamab.
The cORR was 41.3% (95% CI, 30.4-52.8), the median duration of response was 14.9 months (95% CI, 7.4-24.0), and the median OS was 15.5 months (95% CI, 10.4-18.7) (Table; Figure, A). At the time of best overall response, zanidatamab responders demonstrated reduced mean (SD) worst pain scores compared with baseline (complete response, −4.0 [not evaluable]; partial response, −1.0 [2.5]), and those with progressive disease reported an increase (2.4 [2.9]); 59 patients (74%) completed the question at both assessments.
JAMA Oncology , résumé, 2025