e16178 Background: For advanced biliary tract cancer (BTC) patients who failed first-line chemotherapy, second-line options are very limited, especially for those without specific genetic mutations. This study aimed to evaluate the efficacy and safety of the combination of cadonilimab with liposomal irinotecan plus fluorouracil and leucovorin for second or more line treatment of advanced BTC. Methods: This is an interim analysis (data cutoff: December 26, 2025) of a prospective, dual-cohort, phase II trial. Fifty-one locally advanced or metastatic BTC patients who failed at least first-line systemic gemcitabine based chemotherapy with or without PD-L1/PD-1 inhibitor (Cohort 1, prior ICI exposure and Cohort 2, ICI-naïve), were planned to be enrolled. Eligible participants will receive cadonilimab at a dosage of 6 mg/kg combined with intravenous liposomal irinotecan at a dosage of 70 mg/m 2 plus leucovorin at a dosage of 400 mg/m 2 and fluorouracil at a dosage of 2400 mg/m 2 for 46 h every 2 weeks, up to 12 cycles. Patients will receive maintenance cadonilimab up to 24 months if disease stable or remission after combination therapy.The primary endpoint is overall response rate (ORR). The secondary endpoints include overall survival (OS), progression-free survival (PFS), adverse event (AE) incidence rate. Results: Between August 30, 2024 and December 26, 2025, a total of 24 patients were enrolled. Of these,17 patients (Cohort 1: n = 10; Cohort 2: n = 7) with tumor assessment were included in this analysis. The median follow-up was 10.9 months (range, 1.9-11.4). In Cohort 1, the ORR was 30.0% (3/10) and the DCR was 60.0% (6/10). In Cohort 2, the ORR was 28.6% (2/7) and the DCR was 71.4% (5/7). For the overall population (n = 17), the ORR was 29.4% and DCR was 64.7%. The median progression-free survival (PFS) for the combined population was 4.7 months (95% CI, 2.2-NA). By cohort, median PFS was 3.0 months (95% CI, 2.2-NA) in Cohort 1 and was not reached in Cohort 2. The median overall survival (OS) for the combined population was 9.1 months (95% CI, 7.5-NA). By cohort, median OS was 7.7 months (95% CI, 6.4-NA) in Cohort 1 and was not reached in Cohort 2. Treatment-related adverse events (TRAEs) occurred in 100% of the 17 assessed patients, with Grade ≥3 TRAEs reported in 58.8%. The most common Grade ≥3 TRAEs were leukopenia (5/17, 29.4%), neutropenia (5/17, 29.4%), and anemia (2/17, 11.8%). Immune-related adverse events (irAEs) were noted in 52.9% of patients, including rash (5/17, 29.4%), hypothyroidism (3/17, 17.6%), and cardiac events (2/17, 11.8%). Conclusions: In this interim analysis, the combination of cadonilimab with liposomal irinotecan plus fluorouracil and leucovorin shows preliminary signs of efficacy and tolerable toxicity for later-line treatment in advanced BTC. These findings warrant further investigation in larger cohorts. Clinical trial information: NCT06438822 .
X et al. (Thu,) studied this question.