Study of TAS3681 in Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria

• Male ≥18 years of age
• Histological or cytological evidence of metastatic castrate resistant prostate cancer (excluding neuroendocrine differentiation and small cell histology) who are castration resistant and have:
• Dose escalation: documented progression defined in PCWG3 and/or intolerance to abiraterone and/or enzalutamide therapy, as well as 1 or more chemotherapies.
• Expansion: I. Group A: documented progression after abiraterone or enzalutamide and chemotherapy consisting of no more than 2 prior taxane-based therapies ii. Group B: documented progression after only abiraterone or enzalutamide therapy without any chemotherapy iii. Measurable disease per RECIST 1.1 and/or bone metastases
• ECOG performance status of ≤1 on Day 1 Cycle 1
• Ongoing androgen deprivation with serum testosterone <50 ng/dL
• Expansion Phase only: willingness to undergo baseline core biopsies, if feasible
• Ability to take medication orally
• Adequate organ function
• Agree to use effective contraception during the study and for 30 days after the last dose of TAS3681
• Willing to comply with scheduled visits and procedures

Exclusion Criteria

• QTcF ≥ 450 ms, history of QTc prolongation or predisposition for QTc prolongation or family history of sudden cardiac death or QT prolongation
• 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
• 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
• Presence of cardiac pacemaker or implantable cardioverter-defibrillator
• History or presence of bradycardia or conduction abnormalities
• History or presence of cardiac arrest or unexplained syncope
• Hypokalemia
• History of myocardial infarction or severe unstable angina
• Any medication administered within 2 weeks prior to 1st dose of TAS3681 that is known to prolong the QT interval or be arrhythmogenic
• Received G-CSF, radiotherapy for extended field, anticancer chemotherapy, investigational agents, or major surgery within 4 weeks of study drug administration; receipt of anticoagulant or CYP3A inhibitor within 2 weeks of study drug administration
• Serious illness or medical condition that could affect the safety or tolerability of study treatments
• Received prior treatment with TAS3681
• User of herbal products
• Any condition or reason that in the opinion of the investigator, interferes with the ability of the participant to participate in the trial
• To be eligible to participate in the food effect assessment (Escalation Phase only), participants must not have a history or presence of any clinically significant abnormality involving the gastrointestinal tract and an inability to fast for a minimum of 8 hours