Statistical analysis
DLTs
The sample size of the dose-escalation cohort was based on dose-escalation rules, which was a modified 3 + 3 design. A minimum of three patients were initially enrolled in each cohort to evaluate DLTs. If none of the first three DLT-evaluable patients experienced a DLT, then enrollment of the next cohort could proceed. If a patient experienced a DLT, then the cohort was expanded to six patients to be evaluated for additional DLTs. For the phase 2 dose-expansion cohort, a sample size of 100 patients was calculated to provide 99% power to detect a difference in ORR, with a two-sided significance level of 5%. The primary endpoint of ORR was to be assessed using an exact binomial test at a one-sided 2.5% level of significance, rejecting the null hypothesis of ORR 42%An internal monitoring committee (IMC) gave recommendations for study conduct, based on trial safety data, to ensure enhanced patient safety during study treatment. The IMC consisted of a Medical Monitor chair, who was not associated with the study, and representatives from Clinical Science, Safety Science and Biostatistics, who were all external to the study team.