Trastuzumab plus nivolumab with gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer: a phase 1b/2 trial.

Authors

Choong-Kun Lee, Taek Chung, Il Hwan Kim, Hong Jae Chon, Jin Won Kim, Se Jun Park, Woo Kyun Bae, Junghun Kang, Changhoon Yoo, Dong-Hoe Koo, Sora Kang, Minsuk Kwon, Ju Won Kim, Beodeul Kang, Sejung Park, Woochan Hwang, Chang Ho Ahn, Chang Gon Kim, Hye Jin Choi

Published in

Nature medicine. Sep 22, 2026. Epub Sep 22, 2026.

Abstract

Biliary tract cancers (BTCs) are associated with poor outcomes despite recent incorporation of immune checkpoint inhibitors into first-line chemotherapy. Human epidermal growth factor receptor 2 (HER2) overexpression or amplification defines a therapeutically targetable subset of BTC but its integration into first-line chemoimmunotherapy has not been prospectively evaluated. This multi-institutional, open-label, phase 1b/2 HERBOT study (KCSG-HB23-05) aimed to evaluate first-line HER2-targeted quadruplet regimen consisting of trastuzumab, nivolumab, gemcitabine and cisplatin in participants with HER2-positive advanced BTC. Here the primary endpoint was met with an objective response rate of 55% (95% confidence interval (CI) 38.5-70.7; one complete response and 21 partial responses among 40 participants) and a disease control rate of 95% (95% CI 83.5-99.4); the median duration of response was 12.6 months (95% CI 5.7-not reached). With a median follow-up of 17.0 months, the median progression-free survival was 10.6 months (95% CI 7.8-17.4) and median overall survival was not reached. Two participants (5.0%) underwent curative-intent conversion surgery. Common grade ≥3 treatment-related adverse events included neutropenia (57.5%), anemia (30.0%) and thrombocytopenia (22.5%). Preplanned artificial-intelligence-powered whole-slide image analyses suggested that tumors with higher proportions of HER2 3+ cells were associated with greater clinical benefit. These findings suggest that upfront HER2-targeted therapeutic intensification in BTC may represent a promising direction for future first-line treatment strategies, with relevance to ongoing phase 3 studies. ClinicalTrials.gov identifier: NCT05749900 .

PMID:
42773210
Bibliographic data and abstract were imported from PubMed on 23 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.