Breast Cancer Clinical Trials

• Histologically confirmed diagnosis of HR+, HER2 negative metastatic breast cancer.

• Estrogen receptor (ER) and/or progesterone receptor (PR) expression positivity is defined as at least 10% of tumor cells nuclei positive by immunohistochemistry in the sample on testing.

• HER2 negative: defined as IHC staining of 0 or 1+. If HER2 overexpression is equivocal by IHC, defined as 2+, the tumor must be non-gene amplified by FISH (ratio \<2 and HER2 copy number \<4).

• Progression on treatment with a CDK 4/6 inhibitor and hormonal therapy in the metastatic setting

‣ The CDK 4/6 inhibitor must be ribociclib or abemaciclib. Patients on palbociclib are not eligible.

⁃ Patient may have been on palbociclib previously but must have been stable on ribociclib or abemaciclib for at least three months prior to enrolling. In this case, the switch from palbociclib to either ribociclib or abemaciclib must have been of toxicity management and not progression of disease.

⁃ Hormonal therapy is defined as an aromatase inhibitor (anastrozole, letrozole, exemestane) or fulvestrant.

⁃ Patients on tamoxifen are not eligible.

⁃ Both men and pre/perimenopausal women must be on ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist.

• Patients must have measurable disease based on RECIST 1.1 criteria.

• Females of child-bearing potential (FOCBP) who engage in intercourse must agree to use adequate contraception (e.g., hormonal or an intrauterine device \[IUD\] or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 weeks following completion of therapy.

⁃ NOTE: A FOCBP is any woman who meets the following criteria:

• Has not undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy

• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)

‣ FOCBP must have a negative serum pregnancy test within 7 days prior to registration.

⁃ Patients must be ≥ 18 years of age at the time of signing consent.

⁃ Patients must have an estimated life expectancy of at least 12 weeks.

⁃ Patients must exhibit an ECOG performance status of 0 or 1.

⁃ Patients must have adequate organ and bone marrow function as defined below:

• Leukocytes (WBC) ≥ 3,000/mcL

∙ Absolute neutrophil count (ANC) ≥ 1000/mcL

∙ Hemoglobin (Hgb) ≥ 7 g/dL

∙ Platelets (PLT) ≥ 100,000/mcL

∙ Total bilirubin \< 1.5 x Institutional upper limit of normal (ULN); ≤ 3.0 x ULN for patients with Gilbert's syndrome

∙ AST (SGOT)/ALT (SGPT) \< 3 x institutional ULN, or \< 5 x ULN if liver metastasis present

∙ Creatinine \< 1.5 Institutional ULN

⁃ Patients with treated brain metastases are eligible if follow-up brain imaging at least 6 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression.

⁃ Patients must have sufficient samples available to meet Menarini Silicon Biosystems (MSB) specimen requirements.

⁃ Patients with known history or current symptoms of cardiac disease, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.

⁃ Patients must have the ability to understand and the willingness to sign a written informed consent document.