具有表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）的患者常常对目前标准第三代EGFR酪氨酸激酶抑制剂（TKI）产生耐药性；目前尚无经批准的靶向治疗用于奥西美替尼耐药情况。本开放标签、剂量递增和剂量扩大的1期试验评估了将EGFR MET双特异性抗体amivantamab与第三代EGFR TKI lazertinib联合应用对EGFR突变NSCLC患者的抗肿瘤活性的潜力。这些患者在进行第三代TKI单药治疗但未行化疗之前，已经在CHRYSALIS E队列中疾病进展。在剂量递增阶段，确定了推荐的2期联合剂量；在剂量扩大阶段，主要终点是安全性和总体反应率，主要次要终点包括无进展生存期和总体生存期。Amivantamab和lazertinib的安全剖面与各自单药的之前经验基本一致，4%的患者出现≥3级不良事件；未发现新的安全信号。对于未进行生物标志物筛选的45名患者的探索性队列，研究者评估的总体反应率的主要终点为36%（95%置信区间为22-51）。中位持续反应时间为9.6个月，中位无进展生存期为4.9个月。下一代测序及免疫组织化学分析确定了高EGFR和/或MET表达作为潜在预测性生物标志物，但需通过前瞻性评估进行验证。ClinicalTrials.gov识别号：NCT02609776 。© 2023. The Author(s).

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776 .© 2023. The Author(s).