Study Design
cancer, intercurrent illness, ≤28
ADVERSE EVENT, DISEASE PROGRESSION, CANCER, ADVERSE EVENT, STAGGERED, REGRESSION
The study was an open-label, nonrandomized, phase I/II dose-escalation study with planned expansion cohorts. In Part A, participants received CB-103 orally on a once daily schedule (28-day cycle length) which could be adapted during escalation to twice daily or intermittent dosing based on pharmacokinetic and safety signals, to determine the MTD or recommended phase II dose (RP2D). Part B was a potential expansion phase at the MTD/RP2D to determine preliminary evidence of antitumor activity and to confirm safety among patients stratified by preselected cancer indications.Part A was based on a two-parameter Bayesian logistic regression model (BLRM) to investigate safety and tolerability of sequentially enrolled dose cohorts of 3–6 patients. The first 2 participants of each cohort were enrolled in a staggered approach with at least 1 day apart between first dosing. Each dose cohort had to complete a DLT assessment period (one treatment cycle, or 28-days for at least 3 patients) and be reviewed by a Cohort Review Committee before opening a subsequent dose cohort. DLT was defined as any grade 3–4 adverse event (AE) or abnormal lab value [according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03] assessed as unrelated to disease progression, intercurrent illness, or concomitant medications that occurred ≤28 days following the first dose of CB-103.Following a 28-day screening period, a starting dose of 13 mg once daily CB-103 was based on nonclinical toxicology and biochemical studies (Supplementary Data) and expected to achieve an exposure area under the curve (AUCSafety was assessed via monitoring of DLTs during the first treatment cycle, and of AEs, physical exam, and clinical lab results (hematology, coagulation, blood chemistry, urinalysis, and cardiac markers) throughout the study (