尽管顺铂加吉西他滨和其他组合改善了晚期胆道癌（BTC）的生存率，但仍然存在大量未满足的医疗需求。本研究旨在评估纳武单抗联合乐伐替尼二线治疗晚期 BTC 的疗效和安全性。纳武单抗 (240 mg) 每两周给药一次。 I 期确定了乐伐替尼的推荐 II 期剂量（20 mg 或 14 mg）。在第二阶段，主要终点是客观缓解率（ORR）。次要终点是疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和安全性。计划样本量为32名患者，功效为80%，单侧α误差为5%，阈值ORR为10%，预期ORR为30%。在I期中，仑伐替尼的推荐剂量确定为六名患者服用 20 mg，出现一种剂量限制性毒性（心肌炎）。在第二阶段，我们招募了 26 名患者。 ORR、DCR、中位 OS 和 PFS 分别为 9.4% [90% 置信区间 (CI) 2.6% 至 22.5%]、53.1%（95% CI 34.7% 至 70.9%）和 6.4 个月（95% CI 4.9-9.7）个月）和 2.5 个月（95% CI 1.5-4.1 个月）。使用抗生素的患者没有观察到任何反应。 3级或4级不良事件为高血压（59.4%）和胆道感染（37.5%）。皮疹 (28.1%) 和甲状腺功能减退症 (21.9%) 被观察为任何级别的免疫介导不良事件。纳武单抗加乐伐替尼在晚期 BTC 中具有可控的安全性，但其在二线治疗中的疗效有限。版权所有 © 2024作者。由爱思唯尔有限公司出版。保留所有权利。

Although cisplatin plus gemcitabine and other combinations have improved the survival of advanced biliary tract cancer (BTC), high unmet medical needs remain. This study aimed to assess the efficacy and safety of nivolumab plus lenvatinib in the second-line treatment for advanced BTC.Nivolumab (240 mg) was administered biweekly. Phase I determined the recommended phase II dose of lenvatinib (20 mg or 14 mg). In phase II, the primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The planned sample size was 32 patients with a power of 80%, a one-sided alpha error of 5%, threshold ORR of 10%, and expected ORR of 30%.In phase I, the recommended dose of lenvatinib was determined to be 20 mg in six patients, with one dose-limiting toxicity (myocarditis). In phase II, we enrolled 26 patients. ORR, DCR, and median OS and PFS were 9.4% [90% confidence interval (CI) 2.6% to 22.5%], 53.1% (95% CI 34.7% to 70.9%), and 6.4 months (95% CI 4.9-9.7 months) and 2.5 months (95% CI 1.5-4.1 months), respectively. No response was observed in patients with the usage of antibiotics. The grade 3 or 4 adverse events were hypertension (59.4%) and biliary tract infection (37.5%). Rash (28.1%) and hypothyroidism (21.9%) were observed as immune-mediated adverse events of any grade.Nivolumab plus lenvatinib had a manageable safety in advanced BTC, but its efficacy in the second-line treatment was limited.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.