Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors

A Phase 1, First In Human, Single-arm, Open-label Study Of Once A Day, Orally Administered Talazoparib (Bmn 673) In Patients With Advanced Or Recurrent Solid Tumors

This is a single-arm, open-label study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of talazoparib in patients with advanced tumors with DNA-repair pathway deficiencies. There will be 2 parts to the study: a dose escalation phase in which the maximum tolerated dose will be defined, and a dose expansion phase.

Inclusion Criteria:

• Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor
• Must have available archived tumor tissue (formalin-fixed paraffin-embedded) [FFPE].
• 18 years of age or older.
• Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) or increased CA-125 (ovarian cancer) or PSA (prostate cancer) and/or CA 19-9 (pancreatic cancer).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Have adequate organ function
• Able to take oral medications.
• Willing and able to provide informed consent.
• Sexually active patients must be willing to use an acceptable method of contraception.
• Females of childbearing potential must have a negative serum pregnancy test at screening.
• Willing and able to comply with all study procedures.

Part 2 Dose Expansion Tumor Types:

• Breast and ovarian cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 4 prior regimens for metastatic disease.
• Prostate or pancreatic cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 2 prior regimens for metastatic disease.
• Small cell lung cancer (SCLC) patients who have received no more than one prior regimen for SCLC.
• Ewing's sarcoma patients who have received no more than 3 prior regimens for metastatic disease.

Exclusion Criteria:

• Part 2 Expansion: Prior treatment with a PARP inhibitor.

• Has history of central nervous system (CNS) metastasis.

  * Exception: In patients with SCLC, history of adequately treated brain metastasis who do not require corticosteroids for management of CNS symptoms.

• Has had major surgery within 28 days before Cycle 1, Day 1.

• Has active peptic ulcer disease.

• Active gastrointestinal tract disease with malabsorption syndrome.

• Pregnant or breastfeeding at screening or planning to become pregnant (in each case, either oneself or one's partner) at any time during the study.