Abstract OT-30-02: Phase II study of talazoparib, a PARP inhibitor, in somatic BRCA1/2 mutant metastatic breast cancer
Authors: Vidula Neelima , Horick Nora , Basile Erin , Blouch Erica , Ellisen Leif W. , Rugo Hope S. , Bardia Aditya 
Published: February 2021

Abstract
Background: PARP inhibitors are currently approved for the treatment of germline BRCA1/2 mutant metastatic breast cancer, and have been shown to improve outcomes and patient quality of life. However, germline BRCA1/2 mutations are observed in 5-10% of breast cancer, limiting the applicability of this well-tolerated therapy. We previously identified that a proportion of patients have somatic BRCA1/2 mutations detected by cell-free DNA (cfDNA), in the absence of germline BRCA1/2 mutations, and have demonstrated that a PARP inhibitor has therapeutic efficacy in a circulating tumor cell-line developed from a patient with a somatic BRCA1 mutation (Vidula, CCR, 2020). We hypothesize that PARP inhibitors may be effective in somatic BRCA1/2 mutant metastatic breast cancer identified via cfDNA.
Trial Design: In this phase II investigator initiated single-arm clinical trial, 30 patients with pathogenic somatic BRCA1/2 mutations detected by cfDNA in the absence of a known germline BRCA1/2 mutation will be treated with talazoparib, a PARP inhibitor, until development of disease progression or unacceptable toxicity. Patients will undergo serial imaging with CT chest, abdomen, and pelvis and bone scan every 12 weeks, and cfDNA collection every 4 weeks.
Eligibility criteria: Patients with metastatic breast cancer that is triple-negative (with receipt of at least 1 prior line of chemotherapy) or hormone receptor positive, HER2 negative (with receipt of at least 1 prior line of hormone therapy or considered inappropriate for hormone therapy) are eligible. Patients must not have received a PARP inhibitor and must not have a germline BRCA1/2 mutation. Any number of prior lines of therapy are allowed. The somatic BRCA1/2 mutation detected in cfDNA must be an established pathogenic variant. Adequate organ function is also required.
Specific Aims: 1. To determine progression-free survival (PFS) by RECIST 1.1 (Primary endpoint), 2. Objective response rate, 3. Safety and tolerability by NCI CTCAE v 5.0, 4. Serial changes in BRCA1/2 mutant allelic frequency in cfDNA, and compare pre- and post-treatment cfDNA results with treatment (Exploratory aim).
Statistical Methods: Patients are being enrolled in a two-stage design, which provides 80% power to demonstrate that the study treatment is associated with “success” (PFS &gt; 12 weeks) in ≥53% patients (4% alpha).
Accrual: Patients are being screened for enrollment at the Massachusetts General Hospital. This study is also opening at other sites in the U.S. including the University of California San Francisco. (NCT03990896)
Funding: This study is funded by Pfizer ASPIRE award and Conquer Cancer Foundation of ASCO Career Development Award. Contact information: Neelima Vidula, MD, Massachusetts General Hospital, nvidula@mgh.harvard.edu
Citation Format: Neelima Vidula, Nora Horick, Erin Basile, Erica Blouch, Leif W. Ellisen, Hope S. Rugo, Aditya Bardia. Phase II study of talazoparib, a PARP inhibitor, in somatic BRCA1/2 mutant metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-30-02.