TY - JOUR
T1 - Safety and efficacy of YK-029A in previously treated EGFR T790M-Mutant NSCLC
T2 - A multi-center phase I trial
AU - Wu, Xinyu
AU - Wan, Rui
AU - Wu, Lin
AU - Zhao, Mingfang
AU - Zhao, Yanqiu
AU - Dai, Xiumei
AU - Zhao, Jun
AU - Liu, Zhe
AU - Xie, Yanyan
AU - Pan, Yueyin
AU - Zhang, Zhihong
AU - Yao, Yu
AU - Yang, Kunyu
AU - Chen, Bi
AU - Wang, Jie
AU - Duan, Jianchun
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/11
Y1 - 2025/11
N2 - Introduction: YK-029A is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Previous studies have shown promising efficacy and tolerability in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutation. Here, we aimed to evaluate the safety and efficacy of YK-029A in previously treated patients with advanced NSCLC harboring the EGFR T790M mutation, with or without accompanying common EGFR-sensitive mutations following prior EGFR-TKIs. Methods: This multi-center phase I clinical trial includes a dose escalation and an expansion phase. Following the traditional 3 + 3 design, patients were administered YK-029A orally at increasing daily doses of 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg in the first dose escalation phase. In the dose expansion phase, participants in cohorts 1, 2, and 3 take daily doses of YK-029A set at 50 mg, 100 mg, and 150 mg. The primary objective was to assess safety, tolerability and efficacy. Results: Safety was evaluated in a total of 42 patients. No dose-limiting toxicity was reported in any of the groups, and the maximum tolerated dose was not determined. Diarrhea, anemia, and rash were the most frequently reported treatment-related adverse events. Forty patients were included in the efficacy analysis. The objective response rate was 62.5%, and the disease control rate was 87.5% across all dose levels. As of the cutoff date on October 31, 2024, the median follow-up time of the study was estimated to be 37.5 months. YK-029A showed median PFS of 13.1 months and median OS of 40.5 months. Conclusions: The results show that YK-029A in pretreated NSCLC patients with EGFR T790M mutations revealed a satisfactory safety profile and generally good tolerability. Additionally, this agent exhibited encouraging anti-tumor efficacy in patients with advanced NSCLC harboring EGFR T790M mutations previously treated with first-/ second-generation EGFR-TKIs.
AB - Introduction: YK-029A is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Previous studies have shown promising efficacy and tolerability in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutation. Here, we aimed to evaluate the safety and efficacy of YK-029A in previously treated patients with advanced NSCLC harboring the EGFR T790M mutation, with or without accompanying common EGFR-sensitive mutations following prior EGFR-TKIs. Methods: This multi-center phase I clinical trial includes a dose escalation and an expansion phase. Following the traditional 3 + 3 design, patients were administered YK-029A orally at increasing daily doses of 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg in the first dose escalation phase. In the dose expansion phase, participants in cohorts 1, 2, and 3 take daily doses of YK-029A set at 50 mg, 100 mg, and 150 mg. The primary objective was to assess safety, tolerability and efficacy. Results: Safety was evaluated in a total of 42 patients. No dose-limiting toxicity was reported in any of the groups, and the maximum tolerated dose was not determined. Diarrhea, anemia, and rash were the most frequently reported treatment-related adverse events. Forty patients were included in the efficacy analysis. The objective response rate was 62.5%, and the disease control rate was 87.5% across all dose levels. As of the cutoff date on October 31, 2024, the median follow-up time of the study was estimated to be 37.5 months. YK-029A showed median PFS of 13.1 months and median OS of 40.5 months. Conclusions: The results show that YK-029A in pretreated NSCLC patients with EGFR T790M mutations revealed a satisfactory safety profile and generally good tolerability. Additionally, this agent exhibited encouraging anti-tumor efficacy in patients with advanced NSCLC harboring EGFR T790M mutations previously treated with first-/ second-generation EGFR-TKIs.
KW - Clinical trial
KW - Epidermal growth factor receptor
KW - Non-small cell lung cancer
KW - Tyrosine kinase inhibitors
UR - https://www.scopus.com/pages/publications/105019110494
U2 - 10.1016/j.lungcan.2025.108764
DO - 10.1016/j.lungcan.2025.108764
M3 - 文章
C2 - 41124837
AN - SCOPUS:105019110494
SN - 0169-5002
VL - 209
JO - Lung Cancer
JF - Lung Cancer
M1 - 108764
ER -
可持续发展目标 3 良好健康与福祉