我们进行了一项试验，以评估纳武单抗和紫杉醇作为二线疗法治疗富含免疫相关生物标志物的晚期胃癌 (AGC) 的有效性和安全性。这项开放标签、单臂、Ib/II 期研究是该研究的一部分在韩国进行的多机构、生物标志物综合伞研究。在 Ib 期，患者每四周在第 1 天和第 15 天接受纳武单抗（3 mg/kg）治疗，并在第 1、8、15 天接受紫杉醇（剂量水平 1，70 mg/m2 或剂量水平 2，80 mg/m2）。在第二阶段，患有 Epstein-Barr 病毒相关、错配修复缺陷或程序性细胞死亡配体 1 阳性 AGC 的患者被纳入。主要终点是推荐的 II 期剂量（RP2D，Ib 期）和无进展生存期（PFS，II 期）。次要终点包括客观缓解率 (ORR)、总生存期 (OS)、安全性和探索性生物标志物分析。选择剂量水平 2 作为 RP2D。在第二阶段，有 48 名患者入组。中位 PFS 和 OS 分别为 3.9 个月和 11.2 个月。 ORR 为 23.3%，中位缓解持续时间为 16.7 个月。 20 名患者（41.7%）发生了 3 级或以上治疗相关不良事件，主要是中性粒细胞减少症。靶向测序显示，RTK/RAS 通路改变或 HLA-A02 超型患者的生存率更高。基线白细胞介素 1 受体拮抗剂水平升高的患者生存率较差。尽管该研究未达到其主要终点，但纳武单抗和紫杉醇治疗 AGC 表现出持久的反应和可控的毒性特征。基因组分析或血浆细胞因子分析可以为选择从免疫治疗联合化疗中获益更多的患者提供信息。© 2023。作者获得国际胃癌协会和日本胃癌协会的独家许可。

We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC).This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m2 or dose level 2, 80 mg/m2) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis.Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival.Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy.© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.