Stereotactic Radiation & Abemaciclib in the Management of HR+/HER2- Breast Cancer Brain Metastases

Inclusion Criteria:

• HR+ breast cancer to fulfill the requirement of HR+ disease, a breast cancer mustexpress (≥ 1%), by immunohistochemistry (IHC), at least 1 of the hormone receptors (estrogen receptor [ER] or progesterone receptor [PR]) as defined in the AmericanSociety of Clinical Oncology (ASCO) / College of American Pathologists (CAP)Guidelines

• To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate,at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHCor in-situ hybridization as defined by the ASCO / CAP Guidelines

• ≤ 15 brain metastases eligible for stereotactic radiation

• Able to swallow oral medications

• Willing to comply with all study procedures and available for duration of the study

• Measurable brain disease per RANO-BM criteria that can be measured in at least onedimension as ≥ 0.5 cm for both intact brain metastases and post-operative cavities

• Eligible for SRS to brain metastases or to the post-operative bed following surgicalresection

• Maximum diameter of the largest intact brain metastases ≤ 4 cm

• Eastern Cooperative Oncology Group performance status 0 to 2

• A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides ofintracranial/extracranial tumor sample (archival or recent) for biomarker evaluationshould be made available and submitted to the central lab for correlative studies.If attempts to obtain archival tissue are unsuccessful the patient may be enrolled.

• Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatmentwill be allowed if active measurable disease has not previously been treated withradiation therapy

• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin)within 7 days of the first dose of abemaciclib

• WOCBP must agree to follow instructions for method(s) of contraception for theduration of treatment with study drug(s), and for three weeks following the lastdose of abemaciclib

• Adequate organ function as defined in protocol

Exclusion Criteria:

• Presence of leptomeningeal disease

• Prior receipt of whole brain radiation therapy

• Prior receipt of abemaciclib in the setting of brain metastases or in the past 6months for the treatment of metastatic disease.

• All toxicities attributed to prior anticancer therapy must have been resolved toGrade 1 (NCI CTCAE Version 5) or baseline before administration of study drug(s)other than: a. Toxicities attributed to prior anticancer therapy that either are notexpected to resolve and/or result in long-lasting sequelae, such as neuropathy afterplatinum-based therapy b. Toxicities that are not expected to interfere with studytreatment, such as fatigue, alopecia, or grade 2 hematologic toxicity

• Women who are pregnant or breastfeeding

• The patient has serious and/or uncontrolled preexisting medical condition(s) that,in the judgment of the investigator, would preclude participation in this study (forexample, interstitial lung disease, severe dyspnea at rest or requiring oxygentherapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min],history of major surgical resection involving the stomach or small bowel, orpreexisting Crohn's disease or ulcerative colitis or a preexisting chronic conditionresulting in baseline Grade 2 or higher diarrhea)

• The patient has active systemic bacterial infection (requiring intravenous [IV]antibiotics at time of initiating study treatment), fungal infection, or detectableviral infection (such as known human immunodeficiency virus positivity or with knownactive hepatitis B or C [for example, hepatitis B surface antigen positive].Screening is not required for enrollment

• The patient has a personal history of any of the following conditions: syncope ofcardiovascular etiology, ventricular arrhythmia of pathological origin (including,but not limited to, ventricular tachycardia and ventricular fibrillation), or suddencardiac arrest

• History of prior malignancy within 2 years prior to screening, with the exception ofthose with a negligible risk of metastasis or death (e.g., 5-year OS of >90%), suchas but not limited to, non-melanoma skin carcinoma, or stage I endometriod uterinecancer, and others at the discretion of the PI.

• Major surgery or significant traumatic injury that has not been recovered from by 14days before the initiation of study drug

• Current or prior participation in a study of an investigational agent orinvestigational device within 2 weeks of first dose of study treatment

• History of allergy or hypersensitivity to any of the study drugs or study drugcomponents

• Prisoners or individuals who are involuntarily incarcerated