A phase II, exploratory trial of cadonilimab (AK104) plus gemcitabine-cisplatin (GC) as a conversion therapy for patients (pts) with unresectable or systemic treatment–failed biliary tract cancer (BTC).

Abstract

e16177 Background: PD-(L)1 inhibitor combined with GC is an established first-line treatment for unresectable BTC. However, most pts still experience disease progression, and no universally accepted second-line regimen exists. Surgery remains the only potentially curative option. Cadonilimab is a tetrameric bispecific antibody both targeting PD-1 and CTLA-4. This study evaluates the efficacy and safety of AK104 plus GC as a conversion therapy for unresectable or systemic treatment-failed BTC pts. Methods: This ongoing single-center phase II trial enrolls two cohorts. Cohort A (treatment-naïve, unresectable) received up to 8 cycles of AK104 (10mg/kg) + GC (Q3W), with imaging every two cycles to assess resectability. Pts converted to resectable undergo surgery followed by AK104 or combined with GC (combination cycles at investigator’s discretion); unresectable pts switch to AK104 monotherapy—all until PD. Primary endpoints were R0 resection rate and OS. Cohort B (prior systemic-therapy failed) received AK104+GC (investigator-determined cycles) followed by AK104 maintenance, with OS as the primary endpoint. Secondary endpoints for both cohorts were PFS, ORR, DCR and safety. Results: As of Nov 2025, 31 pts were enrolled (14 treatment-naïve, 17 systemic therapy-failed), all with ECOG PS 1. Baseline characteristics for treatment-naïve pts: ICC 28.6%, ECC 42.8%, GBC 28.6%, stage III–IV 85.7%; for systemic therapy failed pts: ICC 11.8%, ECC 41.1%, GBC 47.1%, stage III-IV 94.1%, with 94.1% having received prior ICIs plus chemotherapy. Median maximum tumor diameter was ~32 mm in both cohorts. Among 22 evaluable pts (11 per cohort), the overall ORR was 36.4% and mPFS was 4.8 mo (95% CI 2.6-NE); mOS was not reached at a median follow-up of 5.5 mo (95%CI 4.3-11.2). In treatment-naïve unresectable pts, ORR was 54.5% with an R0 conversion rate of 18.2% (2/11), and median PFS and OS were not reached. In systemic therapy-failed pts, ORR was 18.2%, mPFS was 3.3 mo (95% CI 2.0-9.7), and mOS was 6.9 mo (95% CI 4.1-NE). Grade ≥3 TRAEs occurred in 48.4% (15/31) pts. The most common any grade TRAEs were decreased lymphocyte count (55%), decreased white blood cell count (42%), and anemia (42%). No treatment-related deaths occurred. Conclusions: Cadonilimab combined with GC showed promising anti-tumor activity and manageable safety in both unresectable and systemic treatment-failed BTC pts. Longer follow up is required to further evaluate the efficacy and safety. Clinical trial information: MR-31-24-050538. Efficacy outcomes. Evaluable pts n, (%) treatment-naïven=11 systemic therapy-failed n=11 Alln=22 ORR 6（54.5） 2（18.2） 8（36.4） PR 6（54.5） 2（18.2） 8（36.4） SD 3（27.3） 3（27.3） 6（27.3） PD 2（18.2） 6（54.5） 8（36.4） DCR 9（81.8） 5（45.5） 14（63.6） R0 conversion rate 2（18.2） / / mPFS, mo (95%CI range) NR 3.3 (95% CI 2.0–9.7) 4.8 (95% CI 2.6–NE) mOS, mo (95%CI range) NR 6.9 (95% CI 4.1–NE) NR