Cadonilimab combined with gemcitabine and cisplatin in advanced biliary tract cancer (BicureX): A phase II, single-arm clinical trial.

e16239 Background: PD-1 or PD-L1 inhibitors plus chemotherapy as the first-line treatment has been proven to be effective in improving the prognosis of advanced biliary tract cancer (BTC) patients. Methods: In this phase II, single-arm trial, patients with previously untreated, unresectable, locally advanced or metastatic BTC were enrolled, including intrahepatic or extrahepatic cholangiocarcinoma (ICC/ECC) and gallbladder carcinoma (GBC). Participants received Cadonilimab (10 mg/kg, days 1, every three weeks) plus gemcitabine (1000 mg/m 2 , days 1, 8, Q3W), and cisplatin (25 mg/m 2 , days 1, 8, Q3W) for up to eight cycles, followed by Cadonilimab (10 mg/kg, days 1, Q3W) until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR); the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included associations between response, molecular characteristics, and the immune microenvironment. Results: Between June 30, 2023 and January 15, 2025, a total of 65 patients were enrolled, of which 59 patients completed at least one imaging evaluation. 66.1% (39/59) of these patients were diagnosed with ICC, 23.7% (14/59) with GBC, and 10.2% (6/59) with ECC. The median age was 57 years (32-74 years), and 54.2% of the patients were male. Among the 59 evaluable patients, 50 had unresectable disease at the time of initial treatment. In addition, 41(69.5%) patients had metastasis. Among them, 2 (3.4%) patient acheived complete response (CR), 33 (55.9%) patients had partial response (PR) and 17 (28.8%) patients presented with stable disease (SD). The ORR was 59.3% (35/59) and the DCR was 88.1%. The median PFS time was 9.0 months (95%CI: 8.542–9.458) , and the median duration of response (DOR) was 6.43 months (95%CI: 5.17-7.69). The most common treatment-related adverse events (TRAEs) of any grade were anaemia (85%), rash (63.3%) and leukocytopenia (63.3%). Grade 3 or 4 TRAEs were observed in 70% (42/60) of the patients. Two patients developed immune related myocarditis (Grade 4 TRAEs) after medication, which improved after symptomatic treatment. Of the 49 patients who obtained genetic testing, patients were microsatellite stable (MSS), and the median TMB was 3.84 (0-184.32) Muts/Mb. 6 patients had IDH1 mutations, 5 patients had FGFR2 mutations, and 2 patients had HER2 mutations. Conclusions: Cadonilimab plus gemcitabine and cisplatin shown a promising efficacy and acceptable safety profile as first-line treatment for advanced BTC patients. Clinical trial information: NCT05978609 .