A Dose Escalation and Expansion Study of ASP4132 to Subjects With Advanced Refractory Tumors and Lymphoma

Exclusion Criteria

• •Subject has absolute neutrophil count \< 1000/μL, platelet count \< 75,000/μL, and hemoglobin \< 8 g/dL (\< 5 mmol/L) at Screening
• •Subject has total serum bilirubin ≥1.5 times the upper limit of normal (ULN),serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) \> 3 times ULN, or albumin ≤ 3.0 g/dL at Screening.
• •Subject has any abnormalities in serum sodium, potassium, chloride, calcium and magnesium levels ≥ Grade 2 at screening (CTCAE Version 4.03).
• •Subject has a known elevation in serum lactate at screening ˃ 2x institutional ULN
• •Subject has an estimated glomerular filtration rate (eGFr) of \< 60ml/min as calculated by the modification of diet Renal disease (MDRD) Equation.
• •Subject with a QTcF of \> 450 msec in male subjects and \> 470 msec in female subjects on the screening 12 lead ECG.
• •Subject has Neuropathy ≥ Grade 2 at Screening.
• •Subject has Type 1 Diabetes Mellitus or Type 2 Diabetes Mellitus and currently being treated with insulin or sulfonylureas.
• •Subject has concomitant active second malignancies unless remission was achieved at least 3 years prior to study entry and subject is no longer on therapy for the malignancy.
• •Subject has a significant cardiovascular disease
• •Subject has a known history of acute or chronic hepatitis B (HBV), HIV or hepatitis C (HCV) infection.
• •Subject has serious/active bacterial, viral or fungal infection requiring systemic treatment.
• •Subject has significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhea associated with intestinal malabsorption, Crohn's disease, and/or prior surgical procedures affecting absorption or requirement for intravenous (IV) alimentation.
• •Subject has concurrent severe or uncontrolled medical disease or organ system dysfunction which, in the opinion of the Investigators, would limit life expectancy to \< 3 months.
• •Subject has psychiatric disorder or altered mental status that would preclude an understanding of the informed consent process and/or completion of the necessary study procedures.
• •Subject has difficulty swallowing large pills.
• •Subject currently being treated with biguanides or other agents known to increase risk of lactic acidosis.
• •Subject has unavoidable concomitant treatment with any drug known for causing Torsades de Pointes.
• •Subject has had radiotherapy or surgery within the 4 weeks prior to treatment with ASP4132.
• •Subject has not discontinued all previous systemic therapies for cancer including chemotherapy, immunotherapy, or biological therapies for at least 14 days prior to the initiation of ASP4132.
• •Subject has not fully recovered from the acute toxicities (except alopecia) of any prior anti-cancer therapy.
• •Subject requiring concomitant use of strong CYP3A4 inhibitors or inducers.