Talazoparib Monotherapy in PALB2 Mutation Associated Advanced Breast Cancer

NCT04756765 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: IRB-59141BRS0126NCI-2023-01961
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This purpose of this study is to test if talazoparib is safe and evaluate its response to advanced breast cancer associated with mutation of gene called PALB.

Conditions

Breast Cancer; Advanced Breast Cancer

Keywords

PALB2 mutation

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Response to treatment will be assessed as the number and proportion of participants who achieve either a confirmed complete response (CR) or partial response (PR). The outcome is reported as numbers without dispersion. Clinical response will be assessed as follows. CR: Complete disappearance of all clinical evidence of disease PR: Decrease in size or amount of measurable disease lesions Progressive disease (PD): Worsening of lesions; appearance of new lesions; or recurrence of lesions Stable disease (SD): Disease status that is neither CR, PR, nor PD.

  8 weeks +/-1 week

Secondary Outcomes (4)

• Clinical Benefit Rate (CBR)

  8 weeks +/- 1 week

• Progression-free survival (PFS)

  8 weeks +/- 1 week

• Patient-reported Quality of Life (QoL)

  8 weeks +/- 1 week

• Number of participants with Treatment-related Adverse Events ≥ Grade 3

  3 years

Study Arms (1)

Talazoparib Arm

EXPERIMENTAL

Talazoparib 1 mg/day for 24 cycles (28 days per cycle), continuing until withdrawn or discontinued, eg, until RECIST 1.1 progression or unacceptable toxicity.

Drug: Talazoparib Tosylate

Interventions

Talazoparib Tosylate DRUG

Talazoparib1 mg/day is to be administered orally on a continuous dosing schedule.

Also known as: Talzenna, BMN-673

Talazoparib Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic or recurrent HER2 negative breast cancer (IHC or fluorescence in situ hybridization (FISH) per ASCO/CAP guidelines).
• Deleterious or suspected deleterious mutation in PALB2 assessed by Clinical Laboratory Improvement Amendments (CLIA) approved tumor next generation sequencing (NGS) or germline assay.
• Women and men ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• All clinically significant toxic effects of prior cancer therapy resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v 5.0), except alopecia and G2 neuropathy.
• Measurable disease per RECIST v1.115 (CT CAP with contrast and bone scan or positron emission tomography computer tomography (PET/CT) with IV contrast needed within 28 days of Cycle 1 Day 1. If patients have a history of brain metastases, a MRI brain or CT head with contrast is required).
• A minimum 21 day wash out from previous treatment is required.
• No evidence of progression on platinum (e.g., carboplatin or cisplatin) or within 8 weeks of last platinum dose
• Adequate hematologic function
• Absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3)
• Hemoglobin ≥ 9.0 g/dL with last transfusion at least 14 days before Day 1 of study drug
• Platelets ≥ 100,000 cells/μL (≥ 100,000/mm3)
• Adequate hepatic function
• Bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN). Exception: If Gilbert's syndrome; then ≤ 5 times ULN.
• Aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 x ULN; if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤ 5 x ULN

You may not qualify if:

• Breast cancer amenable to curative treatment.
• Prior treatment with a PARP inhibitor.
• Deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 gene mutation. Patients with variants of unknown significance will be eligible.
• Active Brain metastases OR leptomeningeal carcinomatosis. EXCEPTION: Adequately treated brain metastases documented by baseline CT or MRI scan that have not progressed since previous scans and do not require corticosteroids (prednisone 5 mg/day or equivalent allowed) for management of central nervous system (CNS) symptoms. A repeat CT or MRI following the identification of CNS metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases.
• Pregnant or breastfeeding patients.
• Other malignancy that is either active or for which patient has received treatment in the last three years excluding non melanoma skin cancer and carcinoma in situ of the cervix or breast.
• Known active hepatitis B or hepatitis C.
• Investigational agents within 28 days of C1D1.
• Radiation therapy within 14 days of C1D1.
• Major surgery within 21 days of C1D1.
• Concurrent disease or condition that would interfere with study participation or safety, such as any of the following:
• a. Active, clinically significant infection either grade \> 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or requiring the use of parenteral anti microbial agents within 7 days of C1D1.
• Clinically significant bleeding diathesis or coagulopathy.

Sponsors & Collaborators

• Stanford University: lead
• Pfizer: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Melinda Telli

  Stanford Universiy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 16, 2021
• Study Start: February 23, 2023
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)