A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

This is a Phase 1, open label, dose escalation, safety, preliminary efficacy and pharmacokinetic (PK) study of single agent talazoparib in sequential cohorts of adult patients with advanced solid tumors who are resistant to standard therapy or for whom no standard therapy is available. Successive cohorts of patients will receive escalating doses of talazoparib on an outpatient starting from 0.75 mg/day. This study will evaluate 2 dose levels; 0.75 mg and 1.0 mg. Treatment with investigational product will continue until either disease progression, patient refusal, or unacceptable toxicity occurs. The proposed doses, schedule(s), and PK time points may be reconsidered and amended during the study based on the emerging safety and PK data.

In the study overall, up to 18 (minimum 3) patients are expected to be enrolled depending on the observed DLTs.

Inclusion Criteria:

• Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
• ECOG Performance Status 0 or 1.
• Adequate Bone Marrow, Renal and Liver Function.
• Able to take oral medications.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1.
• Serum or urine pregnancy test (for females of childbearing potential) negative at screening.

Exclusion Criteria:

• Patients with known symptomatic brain metastases requiring steroids.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Radiation therapy within 4 weeks prior to the first dose of study treatment.
• Any antitumor systemic cytotoxic therapies and/or treatment with immune modulators within 4 weeks prior to the first dose of study treatment.
• Previous high dose chemotherapy requiring stem cell rescue.
• Prior irradiation to >25% of the bone marrow.
• Active and clinically significant bacterial, fungal, or viral infection
• Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia requiring medication.
• Hypertension that cannot be controlled by medications.
• Participation in other studies involving investigational drug(s) within 4 weeks prior to the first dose of study treatment.
• Other acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and would make the patient inappropriate for entry into this study.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception and for 180 days after the last dose of investigational product.
• Breastfeeding at screening or at any time during study participation.
• Current use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP within 1 week or 5 half lives which ever is longer prior to the first dose of study treatment.