Cadonilimab plus gemcitabine and cisplatin as first-line treatment for unresectable locally advanced or metastatic biliary tract malignancies: the phase II bicureX clinical trial

Immune checkpoint inhibitors plus gemcitabine and cisplatin (GC) are standard first-line treatment for advanced biliary tract cancer (BTC). Here we report BicureX (ChiCTR2300073023), a single-centre, open-label, single-arm phase II trial of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, plus GC for unresectable locally advanced or metastatic BTC. Patients received up to eight combination cycles followed by cadonilimab maintenance. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1); secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Sixty-one patients were enrolled. At a median follow-up of 23.5 months, ORR was 55.7% (34/61; 95% confidence interval, 42.4–68.5%), meeting the prespecified Simon two-stage efficacy criterion. DCR was 85.2%, median DoR 6.1 months, PFS 8.0 months, and OS 15.6 months. Grade ≥3 adverse events (AEs) occurred in 68.9% and grade ≥3 immune-related adverse events (irAEs) in 18.0%; no death was adjudicated as treatment-related. Proteomics identified a post-hoc exploratory three-protein response-associated signal without significance after false discovery rate correction. These findings support further randomized evaluation. Response rates with approved chemoimmunotherapy regimens remain modest in patients with biliary tract cancer (BTC). Here the authors report the results of a phase II study testing the anti-PD1/CTLA4 bispecific antibody cadonilimab in combination with gemcitabine and cisplatin as first-line treatment for unresectable locally advanced or metastatic BTCs.