Ivonescimab Plus Gemcitabine–Cisplatin in Biliary Tract Cancer (BTC): Journal of Hepatology | July 2026

Introduction:

Advanced biliary tract cancer (BTC) carries a poor prognosis, with limited improvements in survival despite the addition of immune checkpoint inhibitors to standard gemcitabine–cisplatin chemotherapy. This phase II trial evaluated ivonescimab, a novel PD-1/VEGF bispecific antibody, combined with chemotherapy as first-line treatment.

Why was this study needed?

• Current first-line immunochemotherapy provides only modest survival benefit.
• Advanced BTC continues to have poor long-term outcomes.
• More effective first-line treatment strategies are urgently needed.
• Biomarkers predicting treatment response remain poorly defined.
• Novel immunotherapy combinations require prospective evaluation.

Results:

• Ivonescimab plus gemcitabine–cisplatin demonstrated impressive antitumor activity, achieving a 66.7% objective response rate, 100% disease control rate, and a median overall survival of 16.8 months.
• The combination showed a manageable safety profile, with predominantly expected hematologic toxicities and no treatment-related deaths.
• MAP2K7 emerged as a potential biomarker of resistance, suggesting a future role in patient selection and development of combination therapies.

Clinical Impact:

This study suggests that ivonescimab-based immunochemotherapy may improve outcomes beyond current first-line standards for advanced biliary tract cancer. Although these encouraging findings require confirmation in randomized phase III trials, they highlight the promise of dual PD-1/VEGF blockade and biomarker-driven precision therapy.

Bottom Line:

Ivonescimab plus gemcitabine–cisplatin demonstrated encouraging efficacy and acceptable safety as first-line therapy for advanced biliary tract cancer. If confirmed in larger trials, it may become a new treatment option, with MAP2K7 serving as a potential biomarker to personalize therapy.