Statistical Analyses
toxicity, tumor, DLTs, overdose
EVENTS, TUMOR
No formal significance level was defined for this study and all analyses were considered descriptive. Five analysis sets were defined: the dose-escalation set included all patients treated in the dose-escalation cohorts who did not miss >4 cumulative days of planned M8891 doses in the first cycle unless they experienced a DLT; the safety analysis set included all patients who received at least one dose of M8891; the pharmacokinetic analysis set included all patients in the safety analysis set without major protocol deviations/violations or events that would affect pharmacokinetics; the pharmacodynamics in WBCs set included all patients who received at least one dose of M8891 and provided a predose and at least one postdose WBC assessment; and the pharmacodynamics in tumor tissue set included all patients who received at least one dose of M8891 and provided tumor tissue at baseline and at the postdose tumor assessment.To assist the SMC in making recommendations on the next dose level and the MTD, the posterior probabilities (2.5%, 25%, 50%, 75%, and 97.5% quantiles) of toxicity were estimated by a BLRM with overdose control. The model was updated with the number of evaluable patients and DLTs observed after completion of the DLT period for each cohort. The target toxicity for the suggested MTD by the BLRM was 30%.For the efficacy analysis, objective response and clinical benefit were summarized and 95% exact Clopper–Pearson confidence intervals (CI) were estimated (Dose proportionality was assessed using the “power model”; the pharmacokinetic endpoints, AUC, and 