Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

This is a first in human, multinational, phase 1, open-label study of TAS3681 in patients
with metastatic castration resistant prostate cancer (mCRPC)evaluating safety, tolerability,
pharmacokinetics and preliminary antitumor activity in patients with mCRPC for which there is
no standard therapy. Eligible patients will either be enrolled in the dose escalation phase
to evaluate safety and determine the maximum tolerated dose for TAS3681 or the expansion
phase in which additional cohorts of patients may be enrolled to further evaluate safety and
preliminary efficacy of TAS3681 at the MTD or at a lower dose.

Approximately 50 evaluable patients will be enrolled in the Dose Escalation Phase and
approximately 80 patients will be enrolled in the Expansion Phase.

Inclusion Criteria:

1. Male > 18 years of age

2. Histological or cytological evidence of metastatic prostate cancer with progression
defined in PCWG3; Scher HI 2015 and intolerance of standard chemotherapy

3. ECOG performance status of < 1 on Day1 Cycle 1

4. Ongoing androgen deprivation with serum testosterone < 50 ng/dl

5. Ability to take medication orally

6. Adequate organ function

7. Willing to comply with scheduled visits and procedures

Exclusion Criteria:

1. QTc > 450ms, history of Qtc prolongation or predisposition for QTc prolongation or
family history of sudden cardiac death or QT prolongation

2. History or presence of heart failure or left ventricular dysfunction with ejection
fraction < 40% within the previous 6 months; if >6 months cardiac function within
normal limits and free of cardiac-related symptoms

3. History or presence of atrial fibrillation , atrial flutter or paroxysmal
supraventricular tachycardia; the presence or history of ventricular arrhythmias
including ventricular fibrillation and ventricular tachycardia

4. Presence of cardiac pacemaker or implantable cardioverter-defibrillator

5. History or presence of bradydysrhythmia or conduction abnormalities

6. History or presence of cardia arrest or unexplained syncope

7. Hypokalemia

8. History of myocardial infarction or severe unstable angina

9. Any medication administered within 4 weeks prior to 1st dose of TAS3681 that is known
to affect QT interval or arrhythmogenic

10. Received any treatments prohibited in this trial

11. Serious illness or medical condition that could affect the safety or tolerability of
study treatments

12. Received prior treatment of TAS3681

13. User of herbal products

14. Any condition or reason that in the opinion of the investigator, interferes with the
ability of the patient to participate in the trial