Treatment
tumor, overdose
REGRESSION, TUMOR
Patients were allocated to receive oral DS-1205c at an assigned dosage of 200, 400, 800, or 1200 mg twice daily (bid; cohorts 1, 2, 3, and 4). The lowest DS-1205c dosage (i.e., 200 mg bid) was based on nonclinical data, while the escalated dosages were guided by a modified continual reassessment method using a Bayesian logistic regression model following the dosage escalation with overdose control principle [Before starting DS-1205c treatment, eligible patients continued to receive their current EGFR TKI (erlotinib, gefitinib, afatinib, or osimertinib) to minimize the likelihood of tumor flare resulting from TKI discontinuation. The last dose of their prior TKI was taken in the morning 1 day before the initial DS-1205c run-in period.During the run-in period (cycle 0), patients received monotherapy with DS-1205c bid at their assigned dose for 1 week. For cycle 1 and beyond, patients received combination treatment with the assigned dose of DS-1205c bid (every 12 h with a meal) and oral osimertinib 80 mg once daily (co-administered with the morning dose of DS-1205c) [