Study was terminated due to delayed recruitment.

This is a multi-institutional, single arm, open label, Phase Ib/II study of abemaciclib in combination with elacestrant in patients with HR+/Her2- breast cancer metastatic to the brain. Patients may have received up to two prior lines of systemic chemotherapy for locally advanced or metastatic disease. There will be no limit on prior use of endocrine therapy including aromatase inhibitors, tamoxifen and fulvestrant, given a documented clinical benefit of elacestrant in this setting.

This is a multi-institutional, Phase Ib/II study in patients with HR+/Her2- breast cancer metastatic to the brain. Patients may have received up to two prior lines of systemic chemotherapy for locally advanced or metastatic disease. There will be no limit on prior use of endocrine therapy including aromatase inhibitors, tamoxifen and fulvestrant, given a documented clinical benefit of elacestrant in this setting. Single agent abemaciclib at a dose of 150 mg twice a day and elacestrant at a dose of 400mg / day will be administered to all patients, with allowances for up to 2 dose reductions due to treatment related toxicities. Patients will be evaluated for treatment emergent adverse events (AEs) during study participation, and toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0. After accrual of first 10 patients, the accrual will be halted and safety analysis (phase IB) will be performed. If response to the combination therapy will be documented in 2 or less patients accrual will be stopped. If at least 3 patients will have a documented response to therapy, accrual will continue to complete Stage 2

Inclusion Criteria:

• Patients will be eligible for inclusion in this study if all of the following criteria apply:

  1. Post-menopausal women with histologically or cytologically diagnosed metastatic HR+/Her2- breast cancer defined as positive for estrogen receptor or progesterone receptor (more than 1% staining by immunohistochemistry, as defined in 2010 ASCO recommendations, Hammond 2010) and negative for HER2 amplification (immunohistochemistry result of 0-1+, or a negative in situ hybridization).

     Post-menopausal status is defined as:

     1. Documented surgical bilateral oophorectomy
     2. Age > 59 years with amenorrhea for > 1 year since last menses
     3. Age < 60 years with amenorrhea for > 1 year since last menses and serum estradiol and FSH in post-menopausal laboratory range.

  2. Patients must have measurable brain metastasis (patients with leptomeningeal disease and measurable parenchymal disease are permitted) with documented intracranial disease progression. One measurable lesion >10mm, or previously irradiated lesion with increase in size by at least 5mm as defined by RANO-BM criteria and revised RECIST criteria (version 1.1, Appendix C). Patients with prior whole brain radiotherapy are permitted.

  3. Prior treatment with up to two lines of systemic chemotherapy for metastatic disease and two weeks from any previous anticancer therapy including biologics and recovered from expected toxicity; at least 4 weeks from major surgery and recovered; at least 3 weeks from radiation affecting more than 25% of bone marrow and recovered; and 2 weeks from other palliative radiation and recovered.

  4. ECOG performance status ≤ 2 (see Appendix B).

  5. Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 14 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy

  6. Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.

  7. The patient has adequate organ function for all of the following criteria, as defined in Table 1 below.

     Table 1: Laboratory Value Guidance to Establish Adequate Organ Function System Laboratory Value Hematologic ANC: >/= 1.5 × 109/L Platelets: >/=100 × 109/L Hemoglobin: >/=8 g/dL

     Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.

     Hepatic Total bilirubin: \