AMMF’s Virtual 2021 European Cholangiocarcinoma Conference

Abstract No 10

Zanidatamab, a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody, in HER2-expressing biliary tract cancer: results from a Ph 1 study (ZW25‑101) and design of a Ph 2b Study HERIZON-BTC-01

 Do‑Youn Oh, MD, PhD1; Shubham Pant, MD2; Erika Hamilton, MD3; Diana Hanna, MD4; Murali Beeram, MD5; Keun‑Wook Lee, MD, PhD6; Yoon‑Koo Kang, MD, PhD7; Jose Chaves, MD8; Seung Tae Kim, MD9; Sun‑Young Rha, MD, PhD10; Rachel Goodwin, MD, MSc, FRCPC11; Christos Vaklavas, MD12; Elena Elimova, MD, MSc, FRCPC13; Milind Javle, MD2; Kanwal Raghav, MD2; Anthony El-Khoueiry, MD4; Cherrise Brownson14; Todd Gray, MSPH14; Joseph Woolery, PharmD, BCOP14; Funda Meric-Bernstam, MD2

1.Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
2.The University of Texas MD Anderson Cancer Center, Houston, TX, US
3.Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN, US
4.USC Norris Comprehensive Cancer Center, Los Angeles, CA, US
5.The START Center for Cancer Care, San Antonio, TX, US
6.Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
7.Asan Medical Center, Seoul, Korea
8.Northwest Medical Specialties, Tacoma, WA, US
9.Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
10.Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
11.University of Ottawa Cancer Centre, Ottawa, ON, Canada
12.Huntsman Cancer Institute of the University of Utah, UT, US
13.Princess Margaret Cancer Centre, Toronto, ON, Canada
14.Zymeworks Inc., Vancouver, BC, Canada


While HER2 is overexpressed in ~5–19% of biliary tract cancers (BTC), including cholangiocarcinoma (CC) and gallbladder cancer (GBC), there is currently no approved HER2-targeted therapy for patients with these cancers. Zanidatamab (ZW25), is being examined as a treatment in patients with advanced or metastatic HER2-expressing cancers, including BTC.


An ongoing Phase 1 study (NCT02892123) that is evaluating zanidatamab in patients with HER2-expressing, advanced or metastatic cancers, including BTC, that has progressed after standard of care. Key endpoints include safety and anti-tumor activity.

As of Nov 16, 2020, 21 patients with HER2-expressing (IHC3+ or IHC2+/FISH+) BTC (GBC [n=12], intrahepatic CC [n=5] and extrahepatic CC [n=4]) were treated with zanidatamab (20 mg/kg Q2W). These patients had received a median of 2 prior systemic therapies (range 1–8), including 5 patients who had received prior trastuzumab. Treatment-related adverse events (AEs) were all Grade 1 or 2 in severity with the most common (occurring in ≥15% patients) being diarrhea (43%) and infusion-related reactions (33%). Tumor shrinkage was observed in the majority (68%) of patients. The confirmed objective response rate (cORR) in response-evaluable patients (n=20) was 40% (8/20), with a disease control rate of 65% (13/20) and a median duration of response (DOR) of 7.4 months (range 3.2–13.1).


An ongoing phase 2b trial (NCT04466891) designed to evaluate the anti-tumor activity and safety of zanidatamab in patients with advanced or metastatic HER2-amplified BTC (Figure).


Zanidatamab was well-tolerated with encouraging and durable anti-tumor activity. Based on results from the Phase 1 study, zanidatamab was granted Breakthrough Therapy designation by the US FDA in November 2020 for patients with previously-treated advanced or metastatic HER2-amplified BTC.

The pivotal HERIZON-BTC-01 study is further evaluating zanidatamab in patients with HER2-amplified advanced or metastatic BTC and is currently enrolling patients.

Corresponding author: Dr. Do‑Youn Oh ([email protected]; Phone: +82-2-2072-0701; Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea)
Sources of support: ZW25-101 study is sponsored by Zymeworks Inc. HERIZON‑BTC‑01 study is sponsored by Zymeworks Inc. and BeiGene, Ltd.

To view the poster, click here

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