Phase II study of nab-paclitaxel and S-1 combined with tislelizumab as first-line treatment for advanced gallbladder cancer: Preliminary results.

Abstract

e14575 Background: Chemotherapy combined with immunotherapy has become the standard treatment for advanced biliary tract adenocarcinoma; however, the objective response rate (ORR) remains below 30%, and the median overall survival (OS) is approximately one year. Gallbladder cancer (GBC) has a poorer prognosis than cholangiocarcinoma. Therefore, further exploration of optimal treatment strategies is warranted. Based on the results of our previous studies, we conducted this study to evaluate the efficacy and safety of adding tislelizumab to nab-paclitaxel and S-1 as first-line treatment in patients with advanced gallbladder cancer. Methods: This was a prospective, single-arm, phase II trial enrolling patients with unresectable or metastatic gallbladder cancer. Patients received nab-paclitaxel, S-1, and tislelizumab (nab-paclitaxel 125 mg/m², intravenous infusion on days 1 and 8; S-1 80-120 mg/day, oral administration twice daily on days 1-14; tislelizumab 200 mg, intravenous administration on day 1; every 3 weeks). The primary endpoint was ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), OS, and safety. Results: Between August 9, 2023 and November 14, 2025, 38 patients were screened, and 32 patients were ultimately enrolled. The median age was 55 years (range, 39-78), with a higher proportion of female patients (65.6%). Disease stage distribution was as follows: stage IIIb in 6 patients, stage IVa in 1 patient, and stage IVb in 25 patients. The liver was the most common metastatic site, observed in 62.5% (20/32) of patients. All 32 patients were evaluated for efficacy. The ORR was 53.1%, and the DCR was 87.5%. Among the six patients with stage IIIb disease, three underwent radical resection of the primary tumor after chemotherapy. As of December 31, 2025, the median follow-up duration was 22.4 months. The estimated median progression-free survival (PFS) was 7.3 months (95% CI, 5.6-9.1). Overall survival (OS) was not reached at the time of analysis, and the 1-year OS rate was 85.2%. The most common grade 3/4 treatment-related adverse events were neutropenia (31.2%), elevated transaminases (15.6%), and diarrhea (12.5%). Grade 3/4 immune-related adverse events occurred in 18.8% of patients, including elevated transaminases (n = 2), rash (n = 2), increased bilirubin (n = 1), and pneumonitis (n = 1). Conclusions: Preliminary results of this prospective phase II study indicate that nab-paclitaxel and S-1 combined with tislelizumab as first-line treatment demonstrates promising efficacy and manageable safety in patients with advanced gallbladder cancer, which warrants further investigation. Clinical trial information: NCT02830606 .