进行了剂量递增和扩展 1/2 期研究（ClinicalTrials.gov，NCT04818333），以评估新型抗体-药物偶联物 SHR-A1811 在预处理 HER2 改变的晚期非小细胞肺癌 (NSCLC) 中的作用。在这里，我们报告第一阶段部分的结果。先前对铂类化疗失败或不耐受的患者被纳入并接受 SHR-A1811 静脉注射，剂量为每 3 周 3.2 至 8.0 mg/kg。剂量递增遵循贝叶斯逻辑回归模型，其中包括过量控制，以及随后选择剂量扩展的耐受水平。总体而言，共有 63 名患者入组，其中 43 名患者接受了 4.8mg/kg 扩展推荐剂量。所有患者均患有 HER2 突变疾病。 8.0mg/kg 剂量组中的一名患者出现了剂量限制性毒性。 29 名患者（46.0%）发生了 ≥ 3 级治疗相关不良事件。 6.4mg/kg 组中的一名患者因间质性肺疾病死亡。截至2023年4月11日，4.8mg/kg队列的客观缓解率为41.9%（95% CI 27.0-57.9），疾病控制率为95.3%（95% CI 84.2-99.4）。中位回复持续时间为 13.7 个月，18 项回复中有 13 项正在进行中。中位无进展生存期为 8.4 个月（95% CI 7.1-15.0）。 SHR-A1811 在预处理的晚期 HER2 突变 NSCLC 中表现出良好的安全性和具有临床意义的疗效。© 2024。作者。

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.© 2024. The Author(s).