First-line tislelizumab plus chemoradiotherapy for patients with advanced biliary tract cancer: A prospective, biomolecular exploratory, phase II trial.

4125 Background: Advanced biliary tract cancer (BTC) characterized by a poor prognosis, and the combination of immunotherapy with conventional chemoradiotherapy offers a promising therapeutic approach. Methods: This phase II study evaluated the efficacy and safety of tislelizumab (an anti-PD-1 antibody) in combination with chemoradiotherapy as a first-line treatment for advanced BTC. The primary endpoints were objective response rate (ORR) and R0 resection rate, and the secondary endpoints included median progression-free survival (mPFS), median overall survival (mOS), and Disease Control Rate (DCR). Biomarker analyses assessed CA19-9 dynamics and immune cell subsets. Results: Among 28 patients, the ORR was 57% (16/28), with a conversion rate of 14% (4/28) and a 100% R0 resection rate (4/4). The median PFS was 14 months and the median OS was 19 months. The regimen exhibited a manageable safety profile, with grade 3 adverse events occurring in 21% (6/28) of patients (2 with drug-induced liver injury and 4 with myelosuppression). No grade 4 events were observed. Reduced CA19-9 levels were significantly correlated with improved OS (p = 0.022) and PFS (p = 0.002). Immunohistochemistry analysis revealed differential expression of CD4, CD103, and PD-1 between responders and non-responders. Notably, high expression of CD103 + CD8 + tissue-resident memory T (TRM) cells and CD103 + CD8 + PD-1 + TRM cells was associated with significantly improved OS. Conclusions: In conclusion, the combination of tislelizumab with chemoradiotherapy demonstrates promising efficacy and acceptable safety in advanced BTC, with CD103 + CD8 + TRM cells identified as a potential predictive biomarker. Clinical trial information: ChiCTR2300070425.