EGFR酪氨酸激酶抑制剂（TKIs）治疗失败后，表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）的治疗选择有限。该多中心开放标签的Ⅱ期研究旨在评估tislelizumab联合化疗（队列1，TIS+chemo）或tislelizumab联合化疗和bevacizumab（队列2，TIS+chemo+ beva）在EGFR突变非鳞状细胞NSCLC患者中的疗效和安全性，这些患者在EGFR TKI治疗中出现进展。本文报告了TIS+chemo队列的主要分析结果。在TIS+chemo队列中，具有EGFR致敏突变且EGFR TKI治疗失败的患者接受tislelizumab联合卡铂和纳-紫杉醇作为诱导治疗，并随后以tislelizumab联合培美曲塞维持治疗。主要终点是1年无进展生存率（PFS）。计划样本量为66例，历史对照为7%，期望值为20%，单侧α为0.05，功效为85%。2020年7月11日至2021年12月13日期间，共纳入了69例患者。截至2022年6月30日，中位随访时间为8.2个月。在62例评估疗效的患者中，估计的1年PFS率为23.8%（90% CI 13.1% to 36.2%），其90%CI的下限高于化疗的历史对照（7%），达到了主要终点。中位PFS为7.6个月（95% CI 6.4 to 9.8）。中位总生存期（OS）尚未到达（95% CI 14.0 to not estimable），1年OS率为74.5%（95% CI 56.5% to 86.0%）。客观缓解率和疾病控制率分别为56.5%（95% CI 43.3% to 69.0%）和87.1%（95% CI 76.1% to 94.3%）。基线时曾进展为一代/二代和三代EGFR-TKIs的患者PFS较一代/二代EGFR-TKIs进展患者更短（中位数分别为7.5个月和9.8个月，p=0.031）。ctDNA阳性患者的PFS较ctDNA阴性患者更短（中位数分别为7.4个月和12.3个月，p=0.031）。未观察到5级治疗相关不良事件（TEAEs）。40.6%（28/69）的患者出现了3-4级TEAEs。5例（7.2%）患者出现了3-4级免疫相关不良事件。该研究达到了TIS+chemo队列的主要终点。在EGFR突变非鳞状细胞NSCLC的EGFR TKI失败后，tislelizumab联合化疗具有可接受的疗效和安全性。©作者（或其雇主）2023。在CC BY-NC下重新使用。不允许商业再利用。由BMJ出版。

Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+ beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported.In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided α of 0.05, and a power of 85%.Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90% CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95% CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3-4 TEAEs occurred in 40.6% (28/69) of patients. Grades 3-4 immune-related AEs occurred in 5 (7.2%) patients.The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for EGFR-mutated non-squamous NSCLC after EGFR TKI failure.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.