A Phase II Clinical Trial of the PARP Inhibitor Talazoparib in BRCA1 and BRCA2 Wild Type Patients With Advanced Triple Negative Breast Cancer and Homologous Recombination Deficiency or Advanced HER2 Negative Breast Cancer or Other Solid Tumors With a Mutation in Homologous Recombination Pathway Genes
Overview
- Phase
- Phase 2
- Intervention
- Talazoparib Tosylate
- Conditions
- Advanced Breast Cancer
- Sponsor
- Melinda Telli
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Objective Response (OR)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The aim of this single-arm phase 2 clinical trial is to evaluate the anti-cancer activity of Talazoparib (also known as BMN 673) in patients with advanced breast cancer with specific genetic or tumor genomic alterations. Patients with either triple-negative or HER2-negative breast cancer are eligible.
Detailed Description
Talazoparib (BMN 673) is a novel, dual-mechanism PARP inhibitor that potently inhibits the PARP enzyme and effectively traps PARP on DNA. Talazoparib has shown promising single-agent anti-tumor efficacy in several BRCA1/2 mutation-associated advanced cancers. The efficacy of PARP inhibition in BRCA1/2 wild-type TNBC with homologous recombination (HR) defects and in breast tumors with mutations in other non-BRCA1/2 HR pathway genes is currently unknown. This phase 2 trial explores the activity of single agent talazoparib in BRCA1/2 wild-type BC patients using an optimal Simon two-stage design. Eligible subjects will be assigned to one of two parallel cohorts: 1) Cohort A: Subjects (n=29) with advanced TNBC with underlying HR defects as assessed by the HRD assay and, 2) Cohort B: Subjects (n=29) with advanced HER2-negative BC with a somatic or germline mutation in a non-BRCA1/2 HR pathway gene. Gene mutations of interest are: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes (FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL).
Investigators
Melinda Telli
Assistant Professor of Medicine
Stanford University
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort A - Triple-negative Breast Cancer
Participants with advanced triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD) based on the Myriad HRD Assay. Participants receive talazoparib 1 mg by mouth daily.
Intervention: Talazoparib Tosylate
Cohort B - HER2-negative solid tumor
Participants with advanced HER2-negative solid tumor with a deleterious hereditary or cancer somatic mutation in one of the following genes: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes. Participants receive talazoparib 1 mg by mouth daily.
Intervention: Talazoparib Tosylate
Outcomes
Primary Outcomes
Objective Response (OR)
Time Frame: up to 24 weeks
Objective response (OR) is a common measure of benefit. OR is defined as the number of participants who achieved complete response (CR) or partial clinical (PR), per the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (v1.1). RECIST Criteria are assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays, as follows: * CR = Disappearance of all target and non-target lesions * PR = ≥30% decrease in the sum of the long diameter of target lesions * OR = CR+PR * Stable disease (SD) = Small changes that do not meet any of the above criteria * Progressive disease (PD) = ≥20% increase in long diameter of target lesions, and/or the appearance of any new lesion(s) The outcome is expressed as the number of participants that achieved either CR or PR within 24 weeks of the start of treatment, a number without dispersion.
Secondary Outcomes
- Clinical Benefit (CB)(up to 24 weeks)
- Progression-free Survival (PFS)(1 year)