NCT05288127

Efficacy of Talazoparib in Asian Metastatic Breast Cancer Patients With a Homologous Recombinant Deficiency (HRD) Signature

Phase II Study to Assess the Efficacy of Talazoparib in Asian Metastatic Breast Cancer Patients With a Homologous Recombinant Deficiency (HRD) Signature

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: University of Malaya · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. A total of 55 evaluable 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. As it may take several weeks to determine if a patient has experienced a response, a temporary pause in the accrual to the trial may be necessary to ensure that enrollment to the second stage is warranted. The purpose of this study is to determine if Talzenna® can help breast cancer patients who have not inherited an altered BRCA gene. We have identified a genetic signature called HRD100 which identifies patients who may respond to Talzenna®. Disease status will be followed by imaging studies at interval of every 12 weeks, until disease progression, start of non-study treatment, withdrawal of consent to study participation, death or end of the study. RECIST 1.1 will be used as the primary endpoint of the response rate. Safety will be monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Appendix 2). Study Treatment will continue until any of the following occurs: 1. Disease progression, as defined by Response Evaluation Criteria in Solid Tumour (RECIST version 1.1); 2. Unacceptable toxicity; 3. Intercurrent illness that necessitates discontinuation of study treatment; 4. Investigator's decision to withdraw the subject, 5. Pregnancy; 6. Major violation to study treatment or procedure requirements; 7. Withdrawal of consent to treatment; 8. Death; 9. End of the study; 10. Other administrative reasons requiring cessation of study treatment. Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the SCHEDULE OF ACTIVITIES (SoA). The study will be conducted in conformance with Good Clinical Practices. The primary objective of the trial is to determine the objective response rate (CR+PR) of the single agent talazoparib in metastatic TNBC patients with enriched HRD signature using RECIST 1.1. Secondary Objective is to determine the progression free survival (PFS) and overall survival (OS) of talazoparib in metastatic TNBC patients. Exploratory Objectives is to evaluate the HRD signature(s) in predicting response to PARP inhibitor in metastatic TNBC patients.

Conditions

• HRD 100 Gene Expression High
• Triple Negative Breast Cancer

Interventions

Type	Name	Description
DRUG	Talazoparib	The recommended dose is 1 mg talazoparib once daily. Patients should be treated until disease progression or unacceptable toxicity occurs. Daily dosing of talazoparib can be interrupted for recovery from toxicity for up to 28 days. For interruptions longer than 28 days, treatment at the same or a reduced dose can be considered based on the if evidence of response or clinical benefit to talazoparib is noted. Missing dose If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time. Dose adjustments: To manage adverse drug reactions, interruption of treatment or dose reduction based on severity and clinical presentation should be considered.

Timeline

• Start date: 2022-03-08
• Primary completion: 2024-06-01
• Completion: 2025-11-01
• First posted: 2022-03-21
• Last updated: 2022-03-21

Locations

1 site across 1 country: Malaysia