An Open-Label Pharmacokinetics and Safety Study of Talazoparib (MDV3800)

A PHASE I OPEN-LABEL PHARMACOKINETICS AND SAFETY STUDY OF TALAZOPARIB (MDV3800) IN PATIENTS WITH ADVANCED SOLID TUMORS AND NORMAL OR VARYING DEGREES OF HEPATIC IMPAIRMENT

This is a trial to investigate the pharmacokinetics (PK) and the safety of talazoparib in patients with advanced solid tumors and impaired hepatic function.

At the end of the study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study. The decision to allow the patient to continue dosing with talazoparib in an open-label extension (OLE) study will be based on potential overall benefit-risk and patient meeting eligibility criteria for OLE.

Inclusion Criteria:

1. Signed and dated Informed Consent Form (by the patient or a legally acceptable representative as per the local regulations).
2. Female or male at least 18 years of age.
3. Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
4. Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
5. Expected life expectancy of ≥ 3 months.
6. Able to swallow the study drug (no contraindication to oral agents).
7. Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
8. Adequate other organ function at screening and enrollment.
9. Female patients of childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception from the time of the first dose of study drug through 7 months after the last dose of study drug.
10. Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 4 months after last dose of study drug.
11. Female patients must not be breastfeeding at screening nor during the study participation until 7 months after the last dose of the study drug.
12. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Treatment within 14 days or five half lives prior to enrollment whichever is longer with any type of systemic anticancer-therapy or any investigational drug
2. Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
3. Major surgery within 28 days prior to enrollment.
4. Serious accompanying cardiac disorder
5. Active known or suspected brain metastasis or active leptomeningeal disease needing treatment
6. Symptomatic or impending spinal cord compression or cauda equine syndrome
7. Has undergone a liver transplant, kidney transplant or nephrectomy.
8. Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.
9. Known myelodysplastic syndrome
10. Seropositive for human immunodeficiency virus (HIV).
11. Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
12. Gastrointestinal disorder affecting absorption.
13. Known or suspected hypersensitivity to any of the talazoparib capsule components.
14. Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor