A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

Phase 1

Inclusion Criteria:

* Histologically confirmed diagnosis of Malignant Pleural Mesothelioma (MPM) or Non-Small Cell Lung Cancer (NSCLC).
* Measurable disease as defined by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) for MPM or the RECIST 1.1 for NSCLC.
* ≥ 20 years of age.
* Provision of written informed consent.
* For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Hemoglobin (Hb) ≥ 9.0 g/dL.
* Neutrophils ≥ 1500/μL.
* Platelets ≥ 100,000/μL.
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5-fold the upper limit of normal range (ULN) \[≤ 5-fold ULN with any liver metastasis\].
* Total bilirubin ≤ 1.5-fold ULN.
* Creatinine clearance (estimated value) ≥ 60 mL/min.
* Life expectancy ≥ 3 months.
* Females of childbearing potential have a negative urine pregnancy test.

Phase 2

Inclusion Criteria:

* Histologically confirmed diagnosis of MPM.
* Treatment naïve and not indicated for resection.
* Measurable disease as defined by the modified RECIST.
* ≥ 20 years of age.
* Provision of written informed consent.
* For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose.
* ECOG Performance Status of 0 or 1.
* Hb ≥ 9.0 g/dL.
* Neutrophils ≥ 1500/μL.
* Platelets ≥ 100,000/μL.
* AST and ALT ≤ 2.5-fold ULN \[≤ 5-fold ULN for patients with any liver metastasis\].
* Total bilirubin ≤ 1.5-fold ULN.
* Creatinine clearance (estimated value) \> 60 mL/min.
* Life expectancy ≥ 3 months.
* Females of childbearing potential have a negative urine pregnancy test.

Both Phase 1 and 2

Exclusion Criteria:

* Prior anti-cancer chemotherapy and radiotherapy.
* Prior hormonal therapy, immunotherapy, thermotherapy, operation.
* Any brain metastasis requiring treatment or symptomatic.
* Active multiple primary cancers.
* Crohn's disease, ulcerative colitis, small intestine resection.
* Abnormal ECGs.
* Prior myocardial infarction.
* Current use of antiarrhythmic medication.
* Uncontrolled concurrent diseases.
* Known severe hypersensitivity to pemetrexed, cisplatin or other drugs containing platinum.
* Women who are pregnant or breastfeeding.
* Received other investigational drugs.
* Unable or unwilling to swallow BBI608 capsules daily.
* Prior treatment with BBI608.
* Ineligible for participation in the study in the opinion of the Investigators.