Overview

Talazoparib in Advanced Breast Cancer Patients With Homologous Recombinant Deficiency

Status:
Recruiting
Trial end date:
2025-05-10
Target enrollment:
0
Participant gender:
Female
Summary
Talazoparib has shown clinical efficacy in breast cancer patients with germline BRCA1 or BRCA2 mutations. Beyond BRCA1 and BRCA2 mutations, it is plausible that talazoparib may have activity in patients with homologous recombination defects (HRD).
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Seoul National University Hospital
Treatments:
Talazoparib
Criteria
Inclusion Criteria:

1. Adults ≥19 years old.

2. Pathologically documented breast cancer that is unresectable or metastatic

3. Tumor with homologous recombination deficiency (HRD) defined by

- Germline or Somatic BRCA1/2 mutation

- Homologous recombination repair (HRR) genes mutation

- HRD detected through RAD51 foci formation functional assay

- HRR genes: ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B,
RAD51C, RAD51D, and RAD54L

4. Previously treated with a taxane, unless this treatment was contraindicated (whether
in recurrent/metastatic setting or in neoadjuvant/adjuvant setting).

5. Previous treatment with platinum therapy in the advanced or metastatic setting is
permitted, provided the patient did not have a progression during the platinum
treatment. If the patient was treated with neoadjuvant or adjuvant platinum therapy,
at least 6 months of disease-free interval is required after the last dose.

6. Documented radiologic progression (during or after most recent treatment or within 6
months after completing adjuvant therapy).

- If the patients had relapsed within 6 months after adjuvant therapy, this will be
counted as a systemic chemotherapy for advanced or metastatic disease.

7. At least 3 weeks has passed since last chemotherapy treatment

8. At least 2 weeks has passed since last hormone therapy or radiation therapy (including
palliative radiation).

9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1

10. At least one measurable lesion that can be accurately assessed at baseline by computed
tomography (CT) (magnetic resonance imaging [MRI] where CT is not feasible) and is
suitable for repeated assessment as per RECIST v.1.1.

11. Male and female subjects of reproductive/childbearing potential must agree to use a
highly effective form of contraception or avoid intercourse during and upon completion
of the study and for at least 7.0 months after the last dose of study treatment.

- This study recommend "Copper T intrauterine device" as a highly effective methods of
contraception (<1% failure rate)

12. Adequate normal organ and marrow function measured within 28 days prior to
administration of study treatment

- Hemoglobin ≥9.0 g/dL

- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

- Platelet count ≥ 75 x 109/L

- Serum bilirubin ≤ 2.0mg/dL [This will not apply to patients with confirmed
Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is
predominantly unconjugated in the absence of hemolysis or hepatic pathology), who
will be allowed only in consultation with their physician.]

- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be ≤5x ULN

- Adequate renal function: Serum creatinine ≤1.5mg/dL or estimated creatinine
clearance >60 mL/min

13. Negative urine pregnancy test within 7 days prior to registration in premenopausal
patients.

14. Ability to understand and comply with protocol during study period

15. Patients should sign a written informed consent before study entry

Exclusion Criteria:

1. Prior treatment PARP inhibitor

2. However, if the patient participated in a clinical trial evaluating adjuvant PARP
inhibitor, patient is allowed to be included in the present study if the patient
recurred 6 months after completing PARP inhibitor. No more than three line of previous
systemic chemotherapy, excluding neo-adjuvant and adjuvant chemotherapy. (No
limitation on hormone therapy. Hormone therapy is not counted as previous line)

3. If there is a standard treatment available for metastatic breast cancer.

4. History of another primary malignancy except for

- Malignancy treated with curative intent and with no known active disease ≥3 years

- contralateral breast cancer

- Adequately treated non-melanoma skin cancer or lentigo malignancy without
evidence of disease

- Adequately treated carcinoma in situ without evidence of disease

5. Patients with GI tract disease resulting in an inability to take oral medication,
malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative
colitis)

6. History of leptomeningeal carcinomatosis

7. Brain metastases or spinal cord compression.

- Patients with symptomatic uncontrolled brain metastases. A scan to confirm the
absence of brain metastases is not required. The patient can receive a stable dose of
corticosteroids before and during the study as long as these were started at least 4
weeks prior to treatment. Patients with spinal cord compression unless considered to
have received definitive treatment for this and evidence of clinically stable disease
for 28 days

8. active infection or immunocompromised patients including tuberculosis (clinical
evaluation that includes clinical history, physical examination and radiographic
findings, and TB testing in line with local practice), hepatitis B , hepatitis C, or
human immunodeficiency virus (positive HIV 1/2 antibodies).

- Subjects with simple HBV carrier, a past or resolved HBV infection (defined as the
presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV RNA.

9. Patients who have a known immediate or delayed hypersensitivity reaction or
idiosyncrasy to drugs chemically related to any of the study agents or their
excipients.

10. Female patients who are pregnant or breastfeeding.

11. Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements.