奥希替尼是一种中枢神经系统 (CNS) 活性、第三代、不可逆、表皮生长因子受体酪氨酸激酶抑制剂 (EGFR-TKI)，可有效、选择性地抑制 EGFR-TKI 致敏和 EGFR T790M 耐药突变，并在 EGFR-TKI 治疗中显示出疗效。突变（EGFRm）非小细胞肺癌（NSCLC）。我们介绍了 TARGET (NCT05526755) 的基本原理和设计，它将评估 5 年辅助奥希替尼治疗完全切除的 EGFRm II 期至 IIIB 期 NSCLC 患者的疗效和安全性。TARGET 是一项 II 期、多国、开放标签、单一药物-手臂研究。年龄≥18岁（台湾≥20岁）且已切除II期至IIIB期非小细胞肺癌的成年人符合资格；允许事先进行辅助化疗。符合条件的患者必须具有局部确认的常见（外显子 19 缺失或 L858R）或罕见（G719X、L861Q 和/或 S768I）EGFR-TKI 敏化突变（单独或组合）。患者将接受奥西替尼 80 毫克每天一次，持续 5 年或直至疾病复发、停药或死亡。主要终点是研究者评估的 5 年无病生存期 (DFS)（常见 EGFR 突变队列）。次要终点包括：研究者评估的第 3 年和第 4 年的 DFS； 3 年、4 年和 5 年总生存率（常见 EGFR 突变队列）； 3 年、4 年和 5 年的 DFS（罕见 EGFR 突变队列）；安全性和耐受性、复发类型和中枢神经系统转移（两个队列）。探索性终点包括：组织/血浆一致性；使用不同的分析方法分析血浆样本中的循环分子以检测微小残留疾病；偶发性肺结节的发病率和随时间的变化。TARGET 目前正在招募，预计将于 2029 年完成。版权所有 © 2023 作者。由爱思唯尔公司出版。保留所有权利。

Osimertinib is a central nervous system (CNS)-active, third generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations, with demonstrated efficacy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We present the rationale and design for TARGET (NCT05526755), which will evaluate the efficacy and safety of 5 years of adjuvant osimertinib in patients with completely resected EGFRm stage II to IIIB NSCLC.TARGET is a phase II, multinational, open-label, single-arm study. Adults aged ≥18 years (Taiwan ≥20 years), with resected stage II to IIIB NSCLC are eligible; prior adjuvant chemotherapy is allowed. Eligible patients must have locally confirmed common (exon 19 deletion or L858R) or uncommon (G719X, L861Q, and/or S768I) EGFR-TKI sensitizing mutations, alone or in combination. Patients will receive osimertinib 80 mg once daily for 5 years or until disease recurrence, discontinuation or death. The primary endpoint is investigator-assessed disease-free survival (DFS) at 5 years (common EGFR mutations cohort). Secondary endpoints include: investigator-assessed DFS at 3 and 4 years; overall survival at 3, 4, and 5 years (common EGFR mutations cohort); DFS at 3, 4, and 5 years (uncommon EGFR mutations cohort); safety and tolerability, type of recurrence and CNS metastases (both cohorts). Exploratory endpoints include: tissue/plasma concordance; analysis of circulating molecules in plasma samples using different profiling approaches to detect minimal residual disease; incidence and change over time of incidental pulmonary nodules.TARGET is currently recruiting, and completion is expected in 2029.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.