Toripalimab in advanced biliary tract cancer

Area of Science:

• Oncology
• Gastroenterology
• Immunotherapy

Background:

• Advanced biliary tract cancers (BTCs) have limited first-line treatment options.
• Gemcitabine combined with platinum/fluorouracil drugs is the current standard of care.
• Novel therapeutic strategies are needed to improve outcomes for advanced BTC patients.

Purpose of the Study:

• To evaluate the safety and efficacy of toripalimab plus gemcitabine and S-1 (GS) as a first-line treatment for advanced BTC.
• To assess progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profile.
• To explore associations between treatment response and biomarkers like PD-L1 expression, tumor mutational burden (TMB), and genetic variations.

Main Methods:

• A single-arm, phase II study enrolled 50 treatment-naïve patients with advanced BTC.
• Patients received toripalimab, gemcitabine, and S-1 (GS) regimen over 21-day cycles.
• Primary endpoint was PFS; secondary endpoints included OS, ORR, duration of response (DOR), and safety. Biomarker analyses were conducted.

Main Results:

• The 6-month PFS rate was 62%, with a median PFS of 7.0 months and median OS of 15.0 months.
• The objective response rate (ORR) was 30.6%, and the disease control rate (DCR) was 87.8%.
• Common treatment-related adverse events (TRAEs) included leukopenia and neutropenia; Grade III/IV irAEs were rare (skin rash, colitis). Negative PD-L1 expression and SMARCA4 mutation were associated with worse survival.

Conclusions:

• Toripalimab plus GS demonstrates encouraging efficacy in improving PFS and OS for advanced BTC.
• The combination therapy exhibits a manageable safety profile, with a low incidence of severe immune-related adverse events.
• This regimen warrants further investigation as a potential first-line treatment option for advanced BTC, with biomarker analysis providing insights into patient selection.