Randomized Phase II Study of Talazoparib Versus Talazoparib Plus Atezolizumab After Palbociclib Combination Endocrine Therapy for Patients with Premenopausal HR+/HER2- Metastatic Breast Cancer Harboring HRD Scar
This study is a prospective, two-arm, randomized phase II study of talazoparib versus talazoparib plus atezolizumab in ER+ premeonopausal women with metastatic breast cancer harboring HRD scar 1st line treatment: GnRH agonist + Aromatase Inhibitor(AI) + Palbociclib 28 days after the last treatment of 1st line treatment(., randomization for 2nd line treatment is conducte to arm A(Talazoparib+Atezolizumab) and arm B(Talazoparib monotherapy)
⁃ For subjects who were enrolled in the 1L treatment part of the study, inclusion criteria 1)-4) should be met.
• For subjects who were not enrolled in the 1L treatment part of the study, all of the following inclusion criteria should be met prior to the study enrollment.
∙ ECOG performance status 0 - 2
‣ Adequate bone marrow function (≥ANC 1,500/ul, ≥platelet 100,000/ul, ≥Hemoglobin 9.0 g/dl)
‣ Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 60 ml/min)
‣ Adequate liver function (≤ serum bilirubin 2.0 mg/dl, ≤ AST/ALT x 3 upper normal limit) If the subject has liver metastasis, AST/ALT x 5 upper normal limit is acceptable
‣ Histologically confirmed metastatic or locally advanced breast cancer that is not amenable to curative surgery, with or without measurable disease. Patients who have stage IV breast cancer at diagnosis (de novo) or have progressed on distant metastatic sites after curative surgery are eligible.
‣ Prior treatment with endocrine-based therapy + CDK4/6 inhibitor for metastatic or inoperable locally advanced breast cancer. Allowed endocrine-based therapy is as below:
∙ A. Aromatase Inhibitor B. For subjects who had disease progression during or after the adjuvant aromatase inhibitor therapy, fulvestrant C. Up to one line of chemotherapy for metastatic or inoperable locally advanced breast cancer is allowed except for platinum based chemotherapy.
‣ Confirmed germline pathogenic BRCA1 and/or BRCA2 mutation or 35 HRD-related gene alterations (see Appendix 16.5)
‣ age \> 19 years
‣ Patient has HER2 IHC0, IHC1+, or ICH2+/ISH-, as determined according to ASCO/CAP guidelines breast cancer
∙ Patient has ER positive and/or PgR positive according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, defined as 1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally
∙ Female patients should be premenopausal. Premenopausal status is defined as either:
• A. Patient had last menstrual period within the last 12 months B. If on tamoxifen within the past 3 months, with a plasma estradiol ≥10 pg/mL and FSH ≤40 IU/l or in the premenopausal range, according to local laboratory definition C. in case of chemotherapy induced amenorrhea, with a plasma estradiol ≥10 pg/mL) and/or FSH ≤40IU/l or in the premenopausal range according to local laboratory definition.
• D. If the subject started ovarian function suppression, above A-C criteria should be met prior to starting ovarian function suppression.
∙ No possibility of pregnancy and/or urine or serum beta-HCG negative
∙ Patients may continue an ongoing bisphosphonate or denosumab therapy.
∙ Patients who agreed to use an effective contraception method or have no childbearing potential
∙ Written informed consent
∙ Patients who agreed to offer tumor tissue and blood for biomarker analysis