Jazz presents OS, longer follow-up data from HERIZON-BTC-01 trial

Jazz Pharmaceuticals announced long-term follow-up results, including the first-ever overall survival findings, from the Phase 2b HERIZON-BTC-01 clinical trial of zanidatamab in previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer. These data was featured at the American Society of Clinical Oncology Annual Meeting in a poster presentation during the Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary session on June 1, 2024. Zanidatamab is a human epidermal growth factor receptor 2-targeted bispecific antibody being studied in multiple solid tumors. For the trial’s primary endpoint, results demonstrated that a confirmed objective response rate by independent central review was maintained at 41.3% and one additional patient achieved a complete response since initial findings were presented at the ASCO Annual Meeting in 2023. The median duration of response, one of the trial’s key secondary endpoints, increased by approximately 2 months to 14.9 months, compared to the previously reported findings. In this data cut, zanidatamab demonstrated a median estimated OS, another secondary endpoint, of 15.5 months in all patients with HER2+ BTC, 18.1 months in patients with IHC 3+ tumors, and 5.2 months in patients with IHC 2+ tumors. Results highlight the clinically meaningful benefits of sustained and durable responses with continued treatment with zanidatamab. Results from this long-term analysis of the Phase 2b HERIZON-BTC-01 trial indicate that zanidatamab monotherapy demonstrated sustained and durable antitumor responses in previously treated patients with HER2-positive unresectable, locally advanced, or metastatic BTC and support the clinically meaningful benefit of continued treatment with zanidatamab. The safety profile in all enrolled patients remained manageable with favorable tolerability compared with the initial analysis. Two patients discontinued treatment due to treatment-related adverse events . The trial evaluated zanidatamab in patients with HER2-positive, locally advanced unresectable, or metastatic BTC who had received prior gemcitabine-containing therapy. Patients with prior HER2-targeted therapy use were excluded from the trial. All patients were required to have centrally confirmed HER2-amplified tumors. Patients were assigned into two cohorts based on tumor IHC status: Cohort 1 included patients who were IHC 2+/3+ and Cohort 2 included patients who were IHC 0/1+. The median duration of follow-up was 21.9 months. Tumors were assessed every 8 weeks per RECIST v1.1. Updated efficacy analyses include only Cohort 1, while safety analyses include Cohorts 1 and 2. As of July 28, 2023, data from HER2-positive BTC patients enrolled in Cohort 1demonstrated that with longer follow-up, the cORR was maintained from the initial analysis, with one additional complete response. Although the trial was not designed to detect treatment effects by HER2 status, as previously reported, in a pre-planned subgroup analysis of cORR by HER2 expression, responses were observed in patients with IHC 3+ tumors and IHC 2+ tumors. A two-month increase in the median DoR to 14.9 months. In patients with IHC3+ tumors, the median DoR was 14.9 months. The DOR in the 1 responder with IHC 2+ tumors was 7.5 months. A median OS of 15.5 months. The median OS in patients with IHC 3+ was 18.1 months. The median OS in patients with IHC 2+ was 5.2 months. Median progression-free survival (PFS) was maintained compared with the initial analysis, which had a data cutoff of October 10, 2022. In patients with IHC 3+ tumors, the median PFS was 7.2 months months. In patients with IHC 2+ tumors, the median PFS was 1.7 months months. As previously reported for Cohorts 1 and 2, zanidatamab demonstrated a manageable and tolerable safety profile, with no new safety signals identified and no deaths that were treatment related. TRAEs leading to dose reductions remained infrequent. Serious TRAEs occurred in eight patients. One patient experienced serious TRAEs since the initial analysis.Treatment discontinuation rate was 2.3% and no additional patients discontinued treatment due to TRAEs since the initial analysis.