Dose-escalating, Safety, Tolerability and PK Study of TAS-119 in Combination With Paclitaxel in Patients With Advanced Solid Tumors

Background and rationale for study:

In nonclinical pharmacology studies TAS-119 significantly enhanced the antitumor activity of
the microtubule stabilizer paclitaxel and TAS-119 is being developed for use in combination
with paclitaxel.

TAS-119 selectively inhibits the kinase inhibitor Aurora A. AurA regulates cell division by
controlling the transition from G2 to M phase. Overexpression of AurA is associated with
resistance to taxanes.

The study will be conducted in two sequential phases:

Dose Escalation Phase with the purpose to determine the maximum tolerated dose and the
recommended Phase 2 dose of TAS-119 given in combination with paclitaxel

An Expansion Phase in which additional patients will be enrolled to further evaluate the
safety and preliminary efficacy of the recommended Phase 2 dose of TAS-119 in combination
with paclitaxel, during which a subgroup of patients will be evaluated for DDI between
paclitaxel and TAS-119 via PK assessment.

Inclusion Criteria:

1. Is a male or female ≥ 18 years of age, that has provided written informed consent.

2. Has histologically or cytologically confirmed advanced, unresectable metastatic solid
tumor(s) for which the patients have no available therapy likely to provide clinical
benefit, or for which paclitaxel is considered a standard of care.

3. Has adequate organ function as defined by the following criteria:

- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤
3.0 × upper limit of normal (ULN); if liver function abnormalities are due to
underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤ 5 × ULN.

- Total serum bilirubin ≤ 1.5 × ULN.

- Absolute neutrophil count ≥ 1,500/mm3 (excluding measurements obtained within 7
days after administration of granulocyte colony-stimulating factor [G-CSF]).

- Platelet count ≥ 100,000/mm3 (IU: ≥ 100 × 109/L) (excluding measurements
obtained within 7 days after a transfusion of platelets).

- Hemoglobin ≥ 9.0 g/dL

- Total serum creatinine ≤ 1.5 × ULN

- Serum albumin ≥ 3.0 mg/dL.

Exclusion Criteria:

1. Previous inability to tolerate any dose of paclitaxel (i.e., the subject required a
paclitaxel dose reduction or discontinuation).

2. Has received any treatments prohibited in this trial within specified time frames

3. Has a serious illness or medical condition(s) that would affect safety or
tolerability of the study treatments

4. Has history of Grade 2 or greater peripheral neuropathy during the 3 months prior to
enrollment.

5. Has known hypersensitivity to TAS-119 or its components.

6. Has known hypersensitivity to Cremophor® EL, paclitaxel or its components.

7. Is a pregnant or lactating female.