Third-generation EGFR TKIs are rapidly being developed for the treatment of NSCLC in patients harboring EGFR T790M mutations. This study evaluated the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, tolerability, and PK, and preliminarily determined the antitumor activity of ES-072 in NSCLC patients with EGFR T790M mutations.

19 patients meeting the inclusion criteria were enrolled in this study, 16 to the dose-escalation phase, and 3 to the dose-expansion phase. The most common adverse events were QT interval prolongation, anemia, mouth ulceration, keratosis, and cough. Safety and tolerability evaluation of ES-072 showed a maximum tolerated dose of 300 mg, and the RP2D dose was therefore 300 mg once daily. PK analysis showed an ES-072 half-life of 24.5 hours and a T max of approximately 4 hours. The total objective response rate and disease control rate were 46.2% and 76.9%, respectively.

The results of this study concluded that ES-072 was safe and well-tolerated in NSCLC patients harboring EGFR T790M mutations, and adverse events were controllable and reversible. An RP2D of 300 mg once daily was determined, and preliminary investigations showed promising antitumor activity.