A Phase I/II Clinical Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs)

时间窗: From Day 1 of Cycle 1 to Day 24 pre-dose examination (23 days)

DLT was defined as an adverse event meeting any of the following that occurred during the DLT evaluation period in any participants given BBI608 with the causal relationship to BBI608 assessed as "Definite," "Probable," or "Possible." The severity of adverse events was graded according to the CTCAE v4.0-JCOG. * Grade 4 neutropenia persisting for ≥ 7 days * Grade ≥ 3 febrile neutropenia persisting for ≥ 5 days * Grade 3 thrombocytopenia requiring platelet transfusions, grade 4 thrombocytopenia * Grade ≥ 3 non-hematotoxicity except the following: 1. Inappetence, nausea, vomiting and electrolyte abnormality which, within 3 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment 2. Diarrhoea and fatigue which, within 5 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment * Other clinically significant signs in the opinion of the investigator

Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP

时间窗: Cycle 1 Day 1 (Cmax only) and Day 23

Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs)

时间窗: Between initial dosing of the investigational drug and final evaluation in the follow-up observation period, about 17 months

An AE is any untoward medical occurrence in a study subject administered an investigational drug and which does not necessarily have a causal relationship with this treatment. A SAE was an AE that met one or more of the following criteria: * Results in death * Is life-threatening * Requires hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability or incapacity * Is a congenital anomaly or birth defect * Is an important medical event that may jeopardize the subject or may require a medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization. An ADR was defined as adverse events assessed to be related to the investigational drug

Phase 1 Part: Area Under the Concentration-time Curve

时间窗: Cycle 1 Day 1 and Day 23

AUC0-12: Area under the concentration-time curve from time zero to 12 hours, AUC0-24: Area under the concentration-time curve from time zero to 24 hours, AUC0-inf: Area under the concentration-time curve from time zero to infinity

Phase 2 Part: Progression-free Survival (PFS)

时间窗: From BBI608 administration to documented PD or death, whichever is earlier, about 17 months

PFS was defined as the time from BBI608 administration to documented PD (as assessed according to the mRECIST or RECIST 1.1) or death, whichever is earlier. The result of imaging assessment by the imaging assessment committee was used for phase 2 part.