HER2-targeted quadruplet achieves 55% response rate in phase 1b/2 biliary tract cancer trial

The multi-institutional, open-label phase 1b/2 HERBOT study (KCSG-HB23-05) evaluated adding HER2-targeted treatment to first-line chemoimmunotherapy for HER2-positive advanced biliary tract cancer. Forty participants received trastuzumab, nivolumab, gemcitabine and cisplatin. The study assessed objective response as its primary endpoint, alongside disease control, response duration, survival and safety.

The primary endpoint was met, with an objective response rate of 55% (95% CI 38.5–70.7), comprising one complete and 21 partial responses. Disease control was 95%, and median response duration was 12.6 months (95% CI 5.7–not reached). At a median follow-up of 17.0 months, median progression-free survival was 10.6 months (95% CI 7.8–17.4), while median overall survival had not been reached. Two participants (5%) underwent curative-intent conversion surgery.

Common grade ≥3 treatment-related adverse events included neutropenia (57.5%), anemia (30%) and thrombocytopenia (22.5%). Preplanned artificial-intelligence-powered whole-slide analyses suggested an association between higher proportions of HER2 3+ tumor cells and greater clinical benefit. The findings support further evaluation of upfront HER2 targeting, but the small, open-label study and lack of a reported comparator prevent conclusions about benefit over existing first-line regimens. Overall survival remains immature.