Zanidatamab (ZW25) in HER2-positive biliary tract cancers (BTCs): Results from a phase I study.

• DOI: 10.1200/jco.2021.39.3_suppl.299
• Publication Date: 2021-01-22T19:59:19Z
• Authors: Funda Meric-Bernstam; Diana L. Hanna; Anthony B. El-Kho...; Yoon-Koo Kang; Do-Youn Oh; Jorge M Chaves; Sun Young Rha; Erika P. Hamilton; Shubham Pant; Milind M. Javle; Kanwal Pratap Sin...; Allison Fortenberry; Todd Gray; Joseph Woolery; Keun Wook Lee
• Keywords: Tolerability

299 Background: Treatment options are limited for patients with unresectable, locally advanced or metastatic BTCs progressing after first line treatment. Standard second chemotherapy yields objective response rates (ORR) of < 10% and median overall survival these is 6 months. Human epidermal growth factor receptor 2 (HER2) overexpression/ amplification observed in 5–19% BTCs. Zanidatamab a bispecific HER2-targeted antibody that has demonstrated durable single agent activity good tolerability range HER2-overexpressing cancers. Methods: In the expansion cohort this phase I study (NCT02892123), primary to characterize safety zanidatamab secondary objectives include evaluation anti-tumor activity. This includes BTC centrally confirmed HER2 overexpression (immunohistochemistry [IHC] 3+ IHC 2+/ fluorescence situ hybridization [FISH]+), disease progression standard care therapy, measurable per RECIST 1.1. administered at previously identified recommended dose 20 mg/kg every weeks (Q2W). Tumors assessed 8 (response ≥ 4 weeks). Results: As data cutoff date (Jul 28, 2020), (median age: 63 years [range, 42–78]) (11 gallbladder cancers, 5 intra- extra-hepatic cholangiocarcinomas) have been treated zanidatamab. The number prior systemic therapies was 2.5 (range, 1–8), including five who had received therapy (trastuzumab). Fourteen (70%) experienced zanidatamab-related adverse events (AEs), all which were grade 1 severity. most common (occurring 20%) AEs diarrhea (n = 9) infusion-related reactions 6). A treatment-related serious AE fatigue reported one patient. Among evaluable 17), ORR 47% 8; 95% confidence interval [CI]: 23, 72), control rate 65% 11; CI: 38, 86) duration 6.6 months (95% 3.2, not estimable). Conclusions: well tolerated promising overexpressing BTC. Based on data, now being evaluated an ongoing global Phase 2b HER2+ progressed treatment gemcitabine-containing regimen (NCT04466891). Clinical trial information: NCT02892123.