Phase II Study to Assess the Efficacy of Talazoparib in Asian Metastatic Breast Cancer Patients With a Homologous Recombinant Deficiency (HRD) Signature
This is an open label, non randomised, investigator-initiated Phase II study of single agent talazoparib (Talzenna®) in metastatic triple negative breast cancer patients with enriched HRD signature. Approximately 55 subjects will be enrolled in this study to examine the efficacy of talazoparib when given orally 1mg daily for days 1 to 28 for up to 28 months. The study will be conducted using the Simon two-stage phase II design, whereby this study will initially enroll 19 patients with RECIST v1.1 measurable disease with enriched HRD signature (stage I). There will be one interim analysis at the end of stage I and if 3 of the 19 have a response, then no further patient will be accrued. If 4 or more of the 19 patients have a response, then accrual would continue to stage II until a total of 55 patients have been enrolled. This study will be conducted in conformance with Good Clinical Practices. Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the Trial Flow Chart.
• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures (including if needed to undergo germline BRCA testing and counselling as per local hospital practice) and availability for the duration of the study.
• Women, aged 18 and above.
• Received either one or two prior systemic treatments for metastatic breast cancer.
• Histologically confirmed metastatic or recurrent triple-negative breast cancer (defined as ER \<1%, PR \<1%, HER2 negative, as per ASCO CAP guidelines).
• Documented disease progression on the most recent therapy.
• Have availability of 10 ml blood for germline BRCA testing if previous record of germline BRCA mutation status is not available.
• If germline BRCA 1 or 2 (1/2) mutation positive, should be among the 5 patients (in Stage I) or 9 patients (in Stage II) with germline BRCA 1/2 mutation positive.
• Can provide archival tumor tissue sample. Note: Formalin-fixed, paraffin embedded (FFPE) tissue blocks or tissues sections (\>30% neoplastic cells, 2 x 10µm tissue curls each in 2 sterile 1.5ml-micro-centrifuge tubes) and 10 unstained slides are needed.
⁃ Can provide one 10ml and one 6-ml blood samples for future biomedical research.
⁃ Has classification as HRD High based on the HRD 100 gene expression analysis (Appendix 4)
⁃ Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1).
⁃ Has adequate organ function as defined below: • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤ 5 × ULN
∙ Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for Gilbert's syndrome)
‣ Calculated creatinine clearance ≥ 30 mL/min by local laboratory or Cockcroft-Gault formula
‣ Hemoglobin ≥ 9.0 g/dL with last transfusion at least 14 days before randomization
‣ Absolute neutrophil count (ANC) ≥ 1500/mm3
‣ Platelet count ≥ 100,000/mm3
⁃ Females of childbearing potential must be willing to use adequate contraception for the course of the study through at least 7 months after the last dose of study drug.
⁃ Patient must be able to swallow pills.