Statistical analyses
toxicity, tumor, DLTs, PK/PD
ADVERSE EVENT, TUMOR, BEST
The Neuenschwander Continual Reassessment Method dose-escalation design has been previously described. Briefly, the dose level with the highest posterior probability of having a DLT rate within the target toxicity range (≥16% and <33%) was recommended for the next cohort. Additionally, following the protocol amendment, dose escalations were limited to 50-mg increments.Adverse events and DLTs were summarized descriptively by dose cohort. Pharmacokinetic parameters of GSK3368715 and its metabolites (GSK3963583 and GSK3983164) were estimated in the PK/PD population (all participants for whom a PK sample was obtained) using a noncompartmental analysis model (WinNonlin version 8.1) and summarized descriptively. Best overall response as per RECIST 1.1 was summarized descriptively by dose cohort. Levels of tumor cell and plasma pharmacodynamic biomarkers were also summarized descriptively.