Tucatinib plus Trastuzumab in Patients with Biliary Tract Cancer and HER2 Expression: Phase 2 Basket Study

March 2022, Vol 3, No 1

Biliary tract cancers have dismal prognosis, and the treatment options are limited. Up to 15% of patients with biliary tract cancer have HER2-positive disease. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor. Preclinical evidence supports the dual inhibition of HER2 and angiogenesis pathways with tucatinib plus trastuzumab. At the 2022 ASCO GI Cancers Symposium, Tanios S. Bekaii-Saab, MD, Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, presented the objectives and design of the cohort of patients with biliary tract cancer in the SGNTUC-019 phase 2 basket study.

SGNTUC-019 is a multicohort, open-label, internatiåonal phase 2 basket study that is evaluating the safety, tolerability, and antitumor activity of tucatinib plus trastuzumab in patients with previously treated, locally advanced, unresectable or metastatic solid tumors, including biliary tract cancer harboring HER2 overexpression or amplification, or activating mutations. The exploratory objective is to identify tumor-specific alterations that are associated with resistance to tucatinib and patient-reported outcomes.

The biliary tract cancer cohort will include 12 patients who are evaluable for response. This cohort will be expanded from 12 patients to 30 patients if more than 2 responses are observed. The key inclusion criteria are age ≥18 years; disease progression during or after ≥1 previous lines of therapy; ECOG performance status ≤1; adequate hepatic, hematologic, renal, and cardiac functions; and no previous exposure to HER2-directed therapy.

HER2 alterations will be assessed by HER2 overexpression or amplification in tumor tissue by previous immunohistochemistry or in situ hybridization, or by HER2 amplification or mutation in a previous or on-study next-generation sequencing (NGS) assay of circulating tumor DNA or tissue from a previous NGS assay.

The primary end point is the overall response rate; the secondary efficacy end points include safety, disease control rate, duration of response, progression-free survival, and overall survival.

Eligible patients will receive oral tucatinib 300 mg twice daily and intravenous trastuzumab 8 mg/kg on cycle 1 day 1, and 6 mg/kg thereafter every 21 days. Disease status assessments will be conducted every 6 weeks for the first 24 weeks, then every 12 weeks. A change from baseline in health-related quality of life will be evaluated every 2 cycles, using the EQ-5D-5L questionnaire.

This basket study is currently enrolling patients in approximately 75 sites within the United States, the European Union, and Asia-Pacific.


Bekaii-Saab TS, Ramos J, Tan Q, Nakamura Y. SGNTUC-019: phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations—biliary tract cancer cohort. Abstract TPS489.

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