Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2–Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study

Author(s): Yoshiaki Nakamura, MD, PhD1; Nobumasa Mizuno, MD, PhD2; Yu Sunakawa, MD, PhD3; Jean-Luc Canon, MD4; Matthew D. Galsky, MD5; Erika Hamilton, MD6; Hidetoshi Hayashi, MD, PhD7; Guy Jerusalem, MD, PhD8; Seung Tae Kim, MD9; Keun-Wook Lee, MD, PhD10; Lionel Aurelien Kankeu Fonkoua, MD11; Bradley J. Monk, MD12; Danny Nguyen, MD13; Do-Youn Oh, MD, PhD14; Alicia Okines, MD, MBChB15; David M. O’Malley, MD16; Paula Pohlmann, MD17; Martin Reck, MD, PhD18; Sang Joon Shin, MD19; Kazuki Sudo, MD, PhD20; Shunji Takahashi, MD, PhD21; Cedric Van Marcke, MD, PhD22; Evan Y. Yu, MD23; Roman Groisberg, MD24; Jorge Ramos, DO25; Sherry Tan, PhD25; Thomas E. Stinchcombe, MD26; and Tanios Bekaii-Saab, MD27
Source: DOI: 10.1200/JCO.23.00606 Journal of Clinical Oncology
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

A Phase II basket study looking at tucatinib + trastuzumab in mBTC, only 30 patients were studied as this is a small subpopulation. However, the results were compelling, with an ORR of 47%. For a 3L patient who has failed gem/cis and FOLFONI, this would be a targeted option to consider.


To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2–positive (HER2+) metastatic biliary tract cancer (mBTC).


SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors. In the biliary tract cancer cohort, patients had previously treated HER2 overexpressing or amplified (HER2+) tumors (identified with local testing) with no prior HER2-directed therapy. The primary end point was confirmed objective response rate (cORR) per investigator assessment. Patients were treated on a 21-day cycle with tucatinib (300 mg orally twice daily) and trastuzumab (8 mg/kg intravenously followed by 6 mg/kg every 3 weeks).


Thirty patients were enrolled. As of data cutoff (January 30, 2023), the median duration of follow-up was 10.8 months. The cORR was 46.7% (90% CI, 30.8 to 63.0), with a disease control rate of 76.7% (90% CI, 60.6 to 88.5). The median duration of response and progression-free survival were 6.0 months (90% CI, 5.5 to 6.9) and 5.5 months (90% CI, 3.9 to 8.1), respectively. At data cutoff, 15 patients (50.0%) had died, and the estimated 12-month overall survival rate was 53.6% (90% CI, 36.8 to 67.8). The two most common treatment-emergent adverse events (TEAEs) were pyrexia (43.3%) and diarrhea (40.0%). Grade ≥3 TEAEs were reported in 18 patients (60.0%), with the most common being cholangitis, decreased appetite, and nausea (all 10.0%), which were generally not treatment related. TEAEs led to treatment regimen discontinuation in one patient, and there were no deaths due to TEAEs.


Tucatinib combined with trastuzumab had clinically significant antitumor activity and was well tolerated in patients with previously treated HER2+ mBTC.

Author Affiliations

1National Cancer Center Hospital East, Kashiwa, Japan; 2Aichi Cancer Center Hospital, Nagoya, Japan; 3St Marianna University Hospital, Kawasaki, Japan; 4Grand Hospital de Charleroi, Charleroi, Belgium; 5Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; 6Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; 7Kindai University Hospital, Osakasayama, Japan; 8CHU de Liege and Liege University, Liege, Belgium; 9Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea; 10Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea; 11Mayo Clinic Rochester, Rochester, MN; 12HonorHealth Research Institute, University of Arizona, Creighton University, Phoenix, AZ; 13City of Hope National Medical Center, Duarte, CA; 14Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea; 15The Royal Marsden NHS Foundation Trust, London, UK; 16The Ohio State University & James Comprehensive Cancer Center, Columbus, OH; 17MD Anderson Cancer Center, Houston, TX; 18Department of Thoracic Oncology, Airway Research Center North, Germany Center for Lung Disease, Grosshansdorf, Germany; 19Severance Hospital, Yonsei University Health System, Seoul, South Korea; 20National Cancer Center, Tokyo, Japan; 21Cancer Institute Hospital of JFCR, Tokyo, Japan; 22Cliniques Universitaires Saint-Luc, Brussels, Belgium; 23Fred Hutchinson Cancer Center/University of Washington, Seattle, WA; 24Merck & Co, Inc, Rahway, NJ; 25Seagen Inc, Bothell, WA; 26Duke Cancer Institute, Durham, NC; 27Mayo Clinic Scottsdale, Scottsdale, AZ

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