Electrolyzed reduced water, which is capable of scavenging reactive oxygen species, is attracting recent attention because it has shown improved efficacy against several types of diseases including diabetes mellitus. Alloxan produces reactive oxygen species and causes type 1 diabetes mellitus in experimental animals by irreversible oxidative damage to insulin-producing b-cells. Here, we showed that electrolyzed reduced water prevented alloxaninduced DNA fragmentation and the production of cells in sub-G1 phase in HIT-T15 pancreatic b-cells. Blood glucose levels in alloxan-induced type 1 diabetes model mice were also significantly suppressed by feeding the mice with electrolyzed reduced water. These results suggest that electrolyzed reduced water can prevent apoptosis of pancreatic b-cells and the development of symptoms in type 1 diabetes model mice by alleviating the alloxan-derived generation of reactive oxygen species.Keywords Electrolyzed reduced water Á Alloxan Á Type 1 diabetes mellitus Á Reactive oxygen species Á HIT-T15 cells

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9014 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. [Table: see text]