Biliary tract cancer (BTC) is a highly aggressive malignancy with limited second-line therapy. We conducted this phase 2 trial to evaluate the efficacy and safety of second-line nab-paclitaxel plus sintilimab in advanced BTC. Histologically confirmed advanced BTC patients with documented disease progression after first-line chemotherapy were enrolled. Subjects received nab-paclitaxel 125 mg/m² on days 1 and 8 plus sintilimab 200 mg on day 1, administered every 3 weeks. The primary end point was the objective response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS), and adverse reactions. Simultaneously, next-generation sequencing, programmed cell death ligand 1 immunohistochemistry and multiplex immunofluorescence of tumor-infiltrating lymphocytes were applied to explore potential biomarkers. Twenty-six subjects were consecutively enrolled. The ORR was 26.9% (7/26), including two complete responses and five partial responses, which met the primary end point. The disease control rate was 61.5% (16/26). The median PFS was 169 days (about 5.6 months, 95% confidence interval [CI] 60–278 days). The median OS was 442 days (about 14.7 months, 95% CI 298–586 days). Grade 3 treatment-related adverse events (TRAEs) were mainly anemia (27%), leukopenia (23%), neutropenia (19%), and peripheral sensory neuropathy (8%). No grade 4 or 5 TRAEs occurred. Biomarker analysis suggested that positive PD-L1 and high proportions of CD8⁺ T-cell infiltration were correlated with improved clinical outcome. Nab-paclitaxel plus sintilimab is a potentially effective and tolerable second-line regimen for advanced BTC that deserves to be studied in large-scale trials. PD-L1 status and CD8⁺ T cell infiltration might be promising biomarkers for efficacy prediction.

中文翻译：

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二线白蛋白结合型紫杉醇联合信迪利单抗治疗晚期胆道癌的疗效及生物标志物分析

胆道癌（BTC）是一种高度侵袭性的恶性肿瘤，二线治疗有限。我们进行了这项 2 期试验，以评估二线白蛋白结合型紫杉醇加信迪利单抗治疗晚期 BTC 的疗效和安全性。组织学证实的晚期 BTC 患者在一线化疗后记录有疾病进展。受试者在第1天和第8天接受白蛋白结合型紫杉醇125 mg/m ²加在第1天接受200 mg信迪利单抗，每3周给药一次。主要终点是客观缓解率（ORR）。次要终点是无进展生存期（PFS）、总生存期（OS）和不良反应。同时，应用新一代测序、程序性细胞死亡配体1免疫组织化学和肿瘤浸润淋巴细胞的多重免疫荧光来探索潜在的生物标志物。连续招募了二十六名受试者。 ORR 为 26.9% (7/26)，包括 2 例完全缓解和 5 例部分缓解，达到主要终点。疾病控制率为61.5%（16/26）。中位 PFS 为 169 天（约 5.6 个月，95% 置信区间 [CI] 60-278 天）。中位 OS 为 442 天（约 14.7 个月，95% CI 298-586 天）。 3级治疗相关不良事件（TRAE）主要是贫血（27%）、白细胞减少（23%）、中性粒细胞减少（19%）和周围感觉神经病变（8%）。没有发生 4 级或 5 级 TRAE。生物标志物分析表明，PD-L1 阳性和高比例的 CD8 ⁺ T 细胞浸润与临床结果的改善相关。白蛋白结合型紫杉醇联合信迪利单抗是治疗晚期 BTC 的一种潜在有效且可耐受的二线治疗方案，值得在大规模试验中进行研究。 PD-L1 状态和 CD8 ⁺ T 细胞浸润可能是疗效预测的有希望的生物标志物。