52P - Cadonilimab in combined with gemcitabine and cisplatin in advanced biliary tract cancer (BicureX): A phase II, single-arm clinical trial

Background

Immunotherapy plus chemotherapy have been proven to be effective in advanced biliary tract cancer (BTC) patients(pts). However, considerable demand still exists for further improvement of prognosis. This trial aims to evaluate the efficacy and safety of Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) plus gemcitabine and cisplatin for pts with advanced BTC in first-line treatment.

Methods

In this trial, 65 pts were enrolled in advanced BTC, including intrahepatic or extrahepatic cholangiocarcinoma (ICC/ECC) and gallbladder carcinoma (GBC). Participants received Cadonilimab (10 mg/kg, Q3W) plus gemcitabine (1000 mg/m², days 1, 8, Q3W), and cisplatin (25 mg/m², days 1, 8, Q3W) for up to eight cycles, followed by Cadonilimab (10 mg/kg, Q3W) until disease progression or unacceptable toxicity. Treatment response was evaluated according to RECIST v1.1 and explored multiple methods, such as 3-D visualization and Spectral computed tomography Scan. The primary endpoint was the objective response rate (ORR); the secondary endpoints were 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

Until April 30, 2024, 43 pts were enrolled, of which 42 pts completed at least one imaging evaluation. 67.5% of these pts were diagnosed with ICC, 20.9% with GBC, and 11.6% with ECC. The median age was 58.4 (32-74 ), and 55.8% of the pts were male. 24 (81.4%) pts had metastasis. Among them, 1 (2.3%) patient achieved CR, 24 (57.1%) pts had PR and 10 (23.8%) pts presented with SD. The ORR was 59.5% (25/42) and the DCR was 83.3%. The most common TRAEs of any grade were anemia (76.7%), rash (74.4%), and leukocytopenia (51.2%). Grade 3 or 4 TRAEs were observed in 72.1% (31/43) of the patients. Of the 35 pts obtained genetic testing, all pts were microsatellite stable, and the median TMB was 3.84 (0-109.44) Muts/Mb. Six pts had IDH1 mutations, 5 pts had FGFR2 mutations, and 2 pts 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 identification

NCT05978609.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.