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

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.

PURPOSE

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).

METHODS

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).

RESULTS

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.

CONCLUSION

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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