Outcomes and statistical analysis
PD, death, SD, tumor
DISEASE PROGRESSION, DISEASE, SECONDARY, TUMOR
The primary endpoint of this trial was AEs according to NCI-CTCAE 5.0. Secondary endpoints included objective response rate (ORR; CR and PR according to RECIST 1.1), the disease control rate (DCR; CR, PR, and stable disease [SD] ≥ 16 weeks according to RECIST 1.1), duration of response (DOR; the time from the first evidence of response until disease progression [PD] or death), time to response (TTR; the time from treatment initiation to the first evidence of verified response), and progression-free survival (PFS; time from treatment initiation to PD or death from any cause).In the dose de-escalation phase, sample sizes for each dose were determined on the basis of the rolling-six design. In the dose-expansion phase, no formal hypothesis testing is pre-defined in this exploratory study. All patients in phase 1 and phase 2 studies were used for the analysis of primary and secondary endpoints. Patient characteristics, safety outcomes, and tumor response are summarized descriptively. Categorical variables are summarized by frequencies (percentage [%]) and continuous variables are summarized by medians (interquartile range [IQR]). Safety was assessed in all patients who received at least one dose of study medication and had at least one safety assessment. Efficacy analyses were assessed in the intention-to-treat population, defined as patients who received at least one dose of study medication. We estimated 95% confidence intervals (CIs) using the Clopper-Pearson method for tumor response. DOR, TTR, and PFS were analyzed by Kaplan–Meier methodology and expressed as medians with 95% CIs. All statistical tests were two-sided, significance set at 