Statistical analysis
The study followed a standard dose-confirmation schema (phase Ib portion) with three patients per cohort (3 + 3 design) for a total of six patients. A two-stage design was performed in the dose-expansion (phase II portion) with a possible total of 40 patients. An overall RR of 25% was considered clinically meaningful. Using a two-stage Simon’s minimax design, the null and alternative hypothesis were H0: p0 < 10% versus Ha: p1 > 25% for the proportion of patients with complete or partial response (PR) by RECIST criteria. Based on the type I error of 5% and the type II error rate of 20%, p0 = 10% and p1 = 25%. Secondary efficacy variables were analyzed using Kaplan–Meier methods, with a corresponding median and a 95% CI.