Tucatinib/Trastuzumab for Previously Treated Patients With HER2-Positive Metastatic Biliary Tract Cancer

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As reported in the Journal of Clinical Oncology by Nakamura et al, findings in a cohort of the phase II SGNTUC-019 basket study showed that tucatinib plus trastuzumab was active in previously treated patients with HER2-positive metastatic biliary tract cancer who had not received prior HER2-targeted therapy.

The basket trial is evaluating tucatinib/trastuzumab in patients with HER2-altered solid tumors.

Study Details

In the international trial, 30 patients with previously treated HER2-overexpressing or -amplified tumors but no prior HER2-directed therapy were enrolled between June 2021 and May 2022. Patients received 21-day cycles of tucatinib at 300 mg twice daily and trastuzumab at 8 mg/kg (loading dose) followed by 6 mg/kg every 3 weeks. A total of 23 patients (76.7%) in the trial were Asian. The primary outcome measure was investigator-assessed confirmed objective response rate.


At data cutoff in January 2023, median follow-up was 10.8 months (range = 1.5–17.1 months). Objective responses were observed in 14 (46.7%, 90% confidence interval [CI] = 30.8%–63.0%) of 30 patients, with complete response seen in 1. Median duration of response was 6.0 months (90% CI = 5.5–6.9 months). An additional nine patients (30.0%) had stable disease, yielding a disease control rate of 76.7% (90% CI = 60.6%–88.5%).


  • Objective response was observed in 47% of patients, and disease control was seen in 77%.
  • Median response duration was 6 months.

Median progression-free survival was 5.5 months (90% CI = 3.9–8.1 months), with estimated rates at 6 and 12 months of 49.8% and 16.1%, respectively. Median overall survival was 15.5 months (90% CI = 6.5–16.7 months), with estimated 6- and 12-month rates of 73.0% and 53.6%, respectively.

Adverse Events

The most common adverse events of any grade were pyrexia (43.3%), diarrhea (40.0%), and infusion-related reaction, increased blood creatinine, and increased alanine aminotransferase (26.7% each). Grade ≥ 3 adverse events occurred in 60.0% of patients, most commonly cholangitis, decreased appetite, and nausea (10% each). Serious adverse events occurred in 43.3% of patients.

Adverse events led to discontinuation of tucatinib in three patients (due to cholangitis, interstitial lung disease, and liver disorder) and to discontinuation of trastuzumab in one (due to interstitial lung disease). No deaths were attributed to adverse events.

The investigators concluded, “Tucatinib combined with trastuzumab had clinically significant antitumor activity and was well tolerated in patients with previously treated HER2-positive metastatic biliary tract cancer.”

Yoshiaki Nakamura, MD, PhD, of the National Cancer Center Hospital East, Chiba, Japan, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Seagen Inc in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit

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