Trastuzumab plus nivolumab with gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer: a phase 1b/2 trial
Year: 2026
Type: article
Study design: Clinical Trial
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 .
Source: Nature Medicine
Institutions: Yonsei University, Yonsei University Health System, Yonsei Cancer Hospital, Inje University Haeundae Paik Hospital, CHA University Bundang Medical Center, CHA University, Seoul National University, Korea University, Seoul National University Bundang Hospital, Korea University Anam Hospital, The Catholic University of Korea Seoul St. Mary's Hospital, Catholic University of Korea, Chonnam National University Hwasun Hospital, Gyeongsang National University, Asan Medical Center, University of Ulsan, Kangbuk Samsung Hospital, Sungkyunkwan University, Chungnam National University, Chungnam National University Hospital, Samsung Medical Center, Lunit (South Korea)
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7213976696