State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Jianchun Duan , Jun Zhao , Li Zhang , Baogang Liu , Xiubao Ren , Mingjun Li , Bo Shen , Liyun Miao , Xiumei Dai , Yueyin Pan , Yupin Li , Yu Yao , Kunyu Yang , Lin Wu , Chengzhi Zhou , Qitao Yu , Yanyan Xie , Shan Zeng , Jie Wang
Background: This study aimed to evaluate the safety and preliminary efficacy of YK-029A, a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in treated or untreated patients with advanced NSCLC. Methods: This dose-escalation and dose-expansion phase 1 trial recruited previously untreated or treated patients with EGFR ex20ins mutant locally advanced or metastatic NSCLC and previously treated patients with EGFR T790M or rare mutations. In dose-escalation phase, patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 50, 100, 150, 200 to 250 mg/day (3+3 design). In dose-expansion phase, patients with EGFR T790M, EGFR ex20ins, or rare mutations were enrolled. The primary objective was safety. Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) were explored. In the treatment-naïve cohort of EGFR ex20ins mutant NSCLC, patients were administered oral YK-029A 200 mg once daily in a 28-day cycle, and efficacy was assessed by the independent review committee. The study was registered (chinadrugtrials.org.cn,CTR20180350). Results: A total of 108 were included in the safety analysis set. DLT did not occur in dose-escalation phase. MTD was not reached. Treatment-emergent adverse events (TEAEs) of any grade and grade≥3 occurred in 106 (98.1%) and 41 (38.0%) patients, respectively. Treatment-related adverse events (TRAEs) of any grade and grade≥3 occurred in 102 (94.4%) and 30 (27.8%) patients, respectively. One patient had liver abscess related to YK-029A and died. Three patients terminated the treatment because of TEAEs. The most common TRAEs were diarrhea (46.3%), anemia (38.0%), and rash (32.4%). For the treatment-naïve EGFR ex20ins mutant cohort, 26 patients were included in the efficacy analysis set. Most patients were adenocarcinoma (96.4%) and at stage IV (85.7%). At the cut-off date on October 30, 2022, 19 patients (73.1%) had partial remission, five patients (19.2%) had stable disease, and two patients (7.7%) developed disease progression. The confirmed objective response rate achieved 73.1% (95% confidence interval [CI], 52.21% to 88.43%). The median progression-free survival was 9.3 months (95% CI, 5.85 to not evaluated). Conclusions: YK-029A was well tolerated and showed preliminary efficacy in treatment-naïve EGFR ex20ins mutant patients with locally advanced or metastatic NSCLC.
Treatment-naïve ex20ins cohort (200 mg) (N=26) | |
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Objective response rate | 73.1% (95% CI, 52.21% to 88.43%) |
Disease control rate | 92.3% (95% CI, 74.87% to 99.05%) |
Median progression-free survival, months | 9.3 (95% CI, 5.85 to NE) |
Median duration of response, months | 7.5 (95% CI, 3.75 to NE) |
12-month overall survival rate | 83.1% (95% CI, 47.17% to 95.53%) |
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