A Study Evaluating Talazoparib in Relapsed Ovarian, Fallopian Tube, and Peritoneal Cancer

• Drug: Talazoparib
  Talazoparib monotherapy 1mg/day orally
  Other Names:

  • MDV3800
  • BMN673
• Drug: Temozolomide
  temozolomide 37.5 mg/m2 on days 1-5 of each cycle

• Experimental: talazoparib
  Cohorts 1A (PARP inhibitor naïve), 2A (PARP inhibitor sensitive), and 3A (PARP inhibitor refractory)
  Intervention: Drug: Talazoparib
• Active Comparator: talazoparib + temozolomide
  Cohorts 1B (PARP inhibitor naïve), 2B (PARP inhibitor sensitive), and 3B (PARP inhibitor refractory)
  Interventions:

  • Drug: Talazoparib
  • Drug: Temozolomide

Inclusion Criteria:

• Women ? 18 years of age and willing and able to provide informed consent
• Relapsed, histologically confirmed ovarian, fallopian tube, and peritoneal cancer. Histologic subtypes include serous, endometrioid, clear-cell, mixed, undifferentiated histology, and carcinosarcoma.
• Sufficient archival tumor tissue available or consent to a fresh tissue biopsy for biomarker analysis. Consent to blood sample collection for biomarker analysis is required.
• Disease progression per RECIST 1.1 during or after the last treatment. Have metastatic disease with at least 1 target tumor lesion measurable per RECIST 1.1 on the screening scan. Lesions used for biopsies cannot be designated as a measurable lesion for RECIST 1.1 assessments.
• Additional criteria for cohort 1 include the following:
• Have a deleterious germline or a somatic BRCA1 or BRCA2 mutation, or a high diagnostic HRD test score (myChoice score ? 42), which represents a loss of DNA repair function based on testing performed at a sponsor-approved laboratory
• Received at least 1 and no more than 3 platinum-based chemotherapy regimens (prior bevacizumab is allowed) and the last dose is ? 28 days before randomization
• No prior PARP inhibitor treatment (COHORT 1 ONLY)
• Additional criteria for cohorts 2 and 3 include the following:
• Received at least 2 platinum-based chemotherapy regimens (including first-line chemotherapy; prior bevacizumab is allowed) and the last dose is ? 28 days before randomization
• Received prior PARP inhibitor treatment as a single agent or in combination therapy regimen and the last dose is ? 28 days before randomization, as follows:
• For cohort 2 only: Received PARP inhibitor treatment for ? 6 months and had a response of CR, PR, or stable disease for ? 6 months
• For cohort 3 only: Received PARP inhibitor treatment for < 6 months with no response (disease progression or stable disease)
• Eastern Cooperative Oncology Group (ECOG) performance status of ? 2.
• Estimated life expectancy of ? 3 months.
• Able to swallow drugs, have no known intolerance to study drugs or excipients, and able to comply with study requirements.

Exclusion Criteria:

• Have not recovered (recovery is defined as National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] grade ? 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
• Use of any investigational agent within 14 days before randomization.
• Had > 2 paracentesis procedures within 28 days before randomization.
• Major surgery within 14 days before randomization.
• Requirement for intravenous alimentation (at the time of randomization).
• Diagnosis of MDS.

• Myriad Genetic Laboratories, Inc.
• Medivation, Inc.