TY - JOUR
T1 - Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01)
T2 - a multicentre, single-arm, phase 2b study
AU - HERIZON-BTC-01 study group
AU - Harding, James J.
AU - Fan, Jia
AU - Oh, Do Youn
AU - Choi, Hye Jin
AU - Kim, Jin Won
AU - Chang, Heung Moon
AU - Bao, Lequn
AU - Sun, Hui Chuan
AU - Macarulla, Teresa
AU - Xie, Feng
AU - Metges, Jean Phillippe
AU - Ying, Jie'er
AU - Bridgewater, John
AU - Lee, Myung Ah
AU - Tejani, Mohamedtaki A.
AU - Chen, Emerson Y.
AU - Kim, Dong Uk
AU - Wasan, Harpreet
AU - Ducreux, Michel
AU - Bao, Yuanyuan
AU - Boyken, Lisa
AU - Ma, Jiafang
AU - Garfin, Phillip
AU - Pant, Shubham
AU - Abou-Alfa, Ghassan
AU - Alfonso, Jorge Adeva
AU - Aglietta, Massimo
AU - Baron, Ari
AU - Beg, Muhammad
AU - Aguirre, Paula Carrasco
AU - Chen, Eric
AU - Cheng, Ying
AU - Gracián, Antonio Cubillo
AU - Dahan, Laetitia
AU - De Braud, Filippo
AU - Fenocchio, Elisabetta
AU - Gbolohon, Olumide
AU - Gillmore, Roopinder
AU - Jary, Marine
AU - Javle, Milind
AU - Jiang, Yixing
AU - Kang, Jung Hun
AU - King, Gentry George
AU - Kundranda, Madappa
AU - Layos, Laura
AU - Li, Daneng
AU - Liang, Tingbo
AU - Lonardi, Sara
AU - Marathe, Omkar
AU - Mondaca, Sebastian
AU - Martin, Andrés J.Muñoz
AU - Park, Joon Oh
AU - Pazo Cid, Roberto
AU - Fernandez, Paula Ribera
AU - Rimassa, Lorenza
AU - Alonso, Rosa Rodriguez
AU - Sadeghi, Saeed
AU - Scott, Aaron
AU - Tan, Benjamin
AU - Tougeron, David
AU - Yan, Qiang
AU - Yin, Xiaoyu
AU - Zhao, Haitao
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/7
Y1 - 2023/7
N2 - Background: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer. Methods: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were assigned into cohorts based on HER2 immunohistochemistry (IHC) score: cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+). Patients received zanidatamab 20 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate in cohort 1 as assessed by independent central review. Anti-tumour activity and safety were assessed in all participants who received any dose of zanidatamab. This trial is registered with ClinicalTrials.gov, NCT04466891, is ongoing, and is closed to recruitment. Findings: Between Sept 15, 2020, and March 16, 2022, 87 patients were enrolled in HERIZON-BTC-01: 80 in cohort 1 (45 [56%] were female and 35 [44%] were male; 52 [65%] were Asian; median age was 64 years [IQR 58–70]) and seven in cohort 2 (five [71%] were male and two [29%] were female; five [71%] were Asian; median age was 62 years [IQR 58–77]). At the time of the data cutoff (Oct 10, 2022), 18 (21%) patients (17 in cohort 1 and one in cohort 2) were continuing to receive zanidatamab; 69 (79%) discontinued treatment (radiographic progression in 64 [74%] patients). The median duration of follow-up was 12·4 months (IQR 9·4–17·2). Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% [95% CI 30·4–52·8]). 16 (18%) patients had grade 3 treatment-related adverse events; the most common were diarrhoea (four [5%] patients) and decreased ejection fraction (three [3%] patients). There were no grade 4 treatment-related adverse events and no treatment-related deaths. Interpretation: Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer. Funding: Zymeworks, Jazz, and BeiGene.
AB - Background: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer. Methods: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were assigned into cohorts based on HER2 immunohistochemistry (IHC) score: cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+). Patients received zanidatamab 20 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate in cohort 1 as assessed by independent central review. Anti-tumour activity and safety were assessed in all participants who received any dose of zanidatamab. This trial is registered with ClinicalTrials.gov, NCT04466891, is ongoing, and is closed to recruitment. Findings: Between Sept 15, 2020, and March 16, 2022, 87 patients were enrolled in HERIZON-BTC-01: 80 in cohort 1 (45 [56%] were female and 35 [44%] were male; 52 [65%] were Asian; median age was 64 years [IQR 58–70]) and seven in cohort 2 (five [71%] were male and two [29%] were female; five [71%] were Asian; median age was 62 years [IQR 58–77]). At the time of the data cutoff (Oct 10, 2022), 18 (21%) patients (17 in cohort 1 and one in cohort 2) were continuing to receive zanidatamab; 69 (79%) discontinued treatment (radiographic progression in 64 [74%] patients). The median duration of follow-up was 12·4 months (IQR 9·4–17·2). Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% [95% CI 30·4–52·8]). 16 (18%) patients had grade 3 treatment-related adverse events; the most common were diarrhoea (four [5%] patients) and decreased ejection fraction (three [3%] patients). There were no grade 4 treatment-related adverse events and no treatment-related deaths. Interpretation: Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer. Funding: Zymeworks, Jazz, and BeiGene.
UR - http://www.scopus.com/inward/record.url?scp=85163384523&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(23)00242-5
DO - 10.1016/S1470-2045(23)00242-5
M3 - Article
C2 - 37276871
AN - SCOPUS:85163384523
SN - 1470-2045
VL - 24
SP - 772
EP - 782
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 7
ER -