Statistical Analyses
DLTs, SD
DISEASE
The RP2D was determined on the basis of the results of the DLT, safety, pharmacokinetic, efficacy, and biomarker analyses. AEs were listed according to Medical Dictionary for Regulatory activities version 24.1 and graded according to CTCAE version 5.0. The DLT evaluable set included all patients in phase Ib who received study drugs as planned in cycle 1 and patients who had DLTs. The safety analysis set included all patients who received at least one dose of E7389-LF or nivolumab. Pharmacokinetic analyses were performed on the pharmacokinetic analysis set (all patients who received at least one dose of E7389-LF or nivolumab and had at least one evaluable concentration datapoint). Noncompartmental pharmacokinetic parameters calculated for eribulin in phase Ib included the maximum plasma concentration of eribulin (CORR [proportion of patients with complete response (CR) or partial response (PR)] and disease control rate (DCR) [CR plus PR plus stable disease (SD) ≥5 weeks after starting treatment on C1D1] were assessed with 95% CI by cohort and in the overall population.Pharmacodynamic changes of plasma biomarkers from baseline (or C1D1) were analyzed in biomarkers in which ≥80% of the samples demonstrated levels above the lower limit of quantification. Changes were assessed using the one-sample Wilcoxon signed-rank test. These biomarkers were of specific interest, as E7389-LF was shown to increase the levels of these vasculature markers in a previous clinical trial (