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

The study consists of two parts and these will be conducted sequentially: Part 1 (dose
escalation) and Part 2 (dose expansion). Subjects will participate in Part 1 or Part 2.

Inclusion Criteria:

- Subject has a life expectancy of more than 3 months

- Subject agrees not to participate in another interventional study while on treatment.

- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

- Female subject must be either:

1. Of non-child bearing potential:

- post-menopausal (defined as at least 1 year without any menses) prior to
Screening,

- or, documented surgically sterile or status post hysterectomy

2. Or, if of childbearing potential,

- agree not to try to become pregnant during the study and for 90 days after
the final study drug administration;

- if heterosexually active must use two forms of birth control

- Male subject and their female spouse/partners who are of childbearing potential must
be using highly effective contraception consisting of two forms of birth control (one
of which must be a barrier method) starting at Screening and continue throughout the
study period and for 90 days after the final study drug administration.

- Subject must have advanced and/or metastatic, histologically or cytologically
documented cancer or lymphomas, for whom there is no available standard therapy shown
to provide clinical benefit.

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 active central nervous system (CNS) metastases not controlled by prior
surgery or radiotherapy (subjects must be off steroids). Subjects with signs or
symptoms suggestive of brain metastasis are not eligible unless brain metastases are
ruled out by brain MRI/CT.

- 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.