{"id":32096,"date":"2023-06-07T13:00:00","date_gmt":"2023-06-07T13:00:00","guid":{"rendered":"http:\/\/01d086fb0cd395824ec7b43a87a3ce37"},"modified":"2024-11-03T15:12:45","modified_gmt":"2024-11-03T15:12:45","slug":"zanidatamab-demonstrates-meaningful-clinical-benefit-with-a-manageable-safety-profile-in-patients-with-treatment-refractory-her2-positive-biliary-tract-cancer","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/zanidatamab-demonstrates-meaningful-clinical-benefit-with-a-manageable-safety-profile-in-patients-with-treatment-refractory-her2-positive-biliary-tract-cancer\/","title":{"rendered":"Zanidatamab Demonstrates Meaningful Clinical Benefit with a Manageable Safety Profile in Patients with Treatment-Refractory, HER2-positive Biliary Tract Cancer"},"content":{"rendered":"

In a global, multicentre, single-arm, phase IIb HERIZON-BTC-01 study, zanidatamab showed meaningful activity, including rapid and durable responses, with a favourable safety profile in the treatment of patients with HER2<\/em>-positive biliary tract cancer with disease progression on previous gemcitabine-based therapy. It is the largest clinical study reported to date for HER2<\/em>-amplified biliary tract cancer. The confirmed objective response rate (ORR) by independent central review in patients with HER2<\/em>-positive tumours was 41.3%.<\/p>\n

Antitumour activity observed for zanidatamab in patients with HER2<\/em>-positive biliary tract cancer compares favourably to historic controls. The findings are reported at 2023 ASCO Annual Meeting on 2 June in Chicago, IL, US along with a simultaneous publication in The Lancet Oncology<\/em> by Dr. Shubham Pant of the MD Anderson Cancer Center in Houston, TX, US, and Dr. James J Harding of the Memorial Sloan Kettering Cancer Center in New York, NY, US, and study colleagues.<\/p>\n

Most patients with biliary tract cancer present with incurable, locally advanced or metastatic disease. In the first-line setting, patients can be treated with palliative cisplatin-gemcitabine or cisplatin-gemcitabine plus durvalumab, which results in improved overall survival (OS) compared with cisplatin-gemcitabine alone. For patients with locally advanced\/metastatic biliary tract cancer who progress after first-line treatment, standard treatment offers limited clinical benefit with modest improvement in survival. Therapies targeting FGFR2<\/em> or IDH1 <\/em>alterations are beneficial for select patients with these specific molecular subtypes of biliary tract cancer.<\/p>\n

The authors also explained in the background that molecular profiling has identified that HER2<\/em> is mutated, amplified, or overexpressed in 19.1\u201331.3% of cases with gallbladder cancer, 17.4\u201318.5% of extrahepatic cholangiocarcinoma, and 3.7\u20134.8% of intrahepatic cholangiocarcinoma. Findings from early clinical studies of small sample sizes suggest that targeting HER2<\/em> alterations with various agents in biliary tract cancer leads to clinical benefit.<\/p>\n

In preclinical studies, a HER2-targeted bispecific antibody, zanidatamab exhibited antitumour activity in HER2<\/em>-driven neoplasia that was superior to both trastuzumab monotherapy and trastuzumab combined with pertuzumab. A phase I study with zanidatamab demonstrated manageable safety with antitumour activity in multiple HER2-expressing or HER2<\/em>-amplified tumour types. The phase I study included a cohort of patients with biliary tract cancer where treatment with 20 mg\/kg zanidatamab once every 2 weeks elicited a confirmed ORR of 38%.<\/p>\n

The HERIZON-BTC-01 study tests the hypothesis that zanidatamab is an active therapy for patients with HER2<\/em>-amplified biliary tract cancer. Patients were recruited at 32 sites in 9 countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2<\/em>-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per RECIST v1.1, and an ECOG performance status of 0 or 1.<\/p>\n

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 ORR in cohort 1 as assessed by independent central review. Antitumour activity and safety were assessed in all participants who received any dose of zanidatamab. This study is ongoing, and is closed to recruitment.<\/p>\n

Between 15 September 2020 and 16 March 2022, 87 patients were enrolled in HERIZON-BTC-01; 80 in cohort 1 from whom 45 (56%) were female and 35 (44%) were male, 52 (65%) were Asian, median age was 64 years and 7 patients were included in cohort 2 of whom 5 (71%) were male and 2 (29%) were female, 5 (71%) were Asian, median age was 62 years. At the time of the data cut-off on 10 October 2022, 18 patients (21%) of whom 17 in cohort 1 and 1 in cohort 2 were continuing to receive zanidatamab. A total, 69 patients (79%) discontinued treatment, of whom 64 (74%) due to radiographic progression.<\/p>\n

The median duration of follow-up was 12.4 months. Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41.3%, 95% confidence interval [CI] 30.4\u201352.8). Among the 33 responders at the data cut-off, 49% had ongoing responses and 82% had a duration of response of \u226516 weeks. Median time to first response was 1.8 month (range, 1.6-5.5). Progression-free survival and OS are being evaluated.<\/p>\n

In both cohorts, treatment-related adverse events (TRAEs) occurred in 72% of patients; TRAEs in \u226510% of patients were diarrhoea (37%) and infusion-related reaction (33%). In total, 16 patients (18%) had grade 3 TRAEs; the most common were diarrhoea (4.6%) and decreased ejection fraction (3.4%). There was no grade 4 TRAEs and no treatment-related deaths. Two patients (2.3%) discontinued zanidatamab due to an adverse event (decreased ejection fraction and non-infectious pneumonitis).<\/p>\n

Continued development of zanidatamab is currently ongoing for the treatment of HER2-positive biliary tract cancer in combination with standard first-line cisplatin\u2013gemcitabine. Additionally, zanidatamab is being evaluated for other HER2-expressing solid tumours, including in a phase III study for first-line treatment of gastro-oesophageal adenocarcinoma.<\/p>\n

This study was funded by Zymeworks, Jazz Pharmaceuticals, and BeiGene.<\/p>\n

References<\/h3>\n