Using talazoparib to treat advanced breast cancer with PALB2 mutations

A Phase 2 Clinical Trial of Talazoparib Monotherapy for PALB2 Mutation Associated Advanced Breast Cancer

This study is testing if the drug talazoparib can help people with advanced breast cancer caused by PALB2 mutations feel better and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Stanford University (Academic / other)
• Drugs / interventions: Radiation, prednisone
• Locations: 1 site (Stanford, California)
• Trial ID: NCT04756765 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of talazoparib monotherapy in patients with advanced breast cancer associated with a PALB2 mutation. The primary objective is to determine if talazoparib can achieve a 30% objective response rate in this patient population. Secondary objectives include assessing safety, progression-free survival, clinical benefit rate, and the role of circulating tumor DNA in characterizing PALB2 mutations. The study also aims to evaluate the quality of life for patients undergoing treatment.

Who should consider this trial

Good fit: Ideal candidates include adults with confirmed metastatic or recurrent HER2 negative breast cancer and a PALB2 mutation.

Not a fit: Patients with HER2 positive breast cancer or those without a PALB2 mutation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced breast cancer linked to PALB2 mutations.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies in breast cancer, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed metastatic or recurrent HER2 negative breast cancer (IHC or fluorescence in situ hybridization (FISH) per ASCO/CAP guidelines).
2. Deleterious or suspected deleterious mutation in PALB2 assessed by Clinical Laboratory Improvement Amendments (CLIA) approved tumor next generation sequencing (NGS) or germline assay.
3. Women and men ≥ 18 years of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. 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.
6. 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).
7. A minimum 21 day wash out from previous treatment is required.
8. No evidence of progression on platinum (e.g., carboplatin or cisplatin) or within 8 weeks of last platinum dose
9. 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)
10. 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
11. Adequate renal function

    * Serum creatinine ≤ 1.5 x ULN; or
    * Calculated creatinine clearance \> 50 mL/min using the Cockcroft Gault formula.
12. Able to take oral medications
13. Received 0 3 prior therapies for advanced disease
14. Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test and be willing to have additional urine pregnancy tests during the study. Women considered not of childbearing potential include those who have had no menstrual period for at least 1 year and have an estradiol in the postmenopausal range, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy or bilateral oophorectomy.
15. WOCBP must agree to use effective contraception as of C1D1 and for 3 months after the last dose.
16. Male participants and their female partners of child bearing potential must be willing to use an appropriate method of contraception during the study and for 3 months after the last dose.
17. Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research related procedures
18. Willing and able to comply with all study procedures
19. Adequate archival or fresh tumor sample from metastatic biopsy site; archival tumor from the primary breast tumor may be submitted if metastatic biopsy is not available and/or infeasible

Exclusion Criteria:

1. Breast cancer amenable to curative treatment.
2. Prior treatment with a PARP inhibitor.
3. Deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 gene mutation. Patients with variants of unknown significance will be eligible.
4. 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.
5. Pregnant or breastfeeding patients.
6. 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.
7. Known active hepatitis B or hepatitis C.
8. Investigational agents within 28 days of C1D1.
9. Radiation therapy within 14 days of C1D1.
10. Major surgery within 21 days of C1D1.
11. 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.
12. Clinically significant bleeding diathesis or coagulopathy.

Where this trial is running

Stanford, California

• Stanford University — Stanford, California, United States (Recruiting)

Study contacts

• Principal investigator: Melinda Telli — Stanford Universiy
• Study coordinator: Nuzhat Shaikh

Conditions Breast Cancer; Advanced Breast Cancer; PALB2 mutation