Neoadjuvant Study of Abemaciclib, Durvalumab, and an Aromatase Inhibitor Early Stage Breast Cancer

Exclusion Criteria

• •1. Any serious preexisting medical condition(s) that would place the patient at increased risk for toxicities including interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel.
• •2. Body weight \< 30 kg (or 66.5 lbs.). If during the study, the patient's weight drops to \< 30 Kg (or 66.5 lbs), they will be withdrawn from the study.
• •3. Females who are pregnant or lactating.
• •4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent
• •5. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are eligible
• •6. History of significant cardiac disease including heart failure, ventricular arrhythmia, or prolonged QT syndrome.
• •7. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline ≥ Grade 2 diarrhea.)
• •8. History of primary immunodeficiency, or subjects who are known to be HIV (Human Immunodeficiency Virus ) positive
• •9. History of organ transplant that requires use of immunosuppressives
• •10. Known allergy or reaction to any of the study drugs.
• •11. Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
• •12. Major surgical procedure (as defined by the investigator) within 30 days prior to the first dose of study drugs or still recovering from prior surgery
• •13. Known history of tuberculosis
• •14. Subjects who are known to be hepatitis B or C positive
• •15. History of prior therapy with a checkpoint (PD-L1/PD-1) including durvalumab or CDK4/6 inhibitor
• •16. History of prior ipsilateral radiation therapy to the cancer-affected breast
• •17. History of prior therapy with an investigational anticancer therapy within 6 weeks prior to the first dose of study drugs
• •18. Prior chemotherapy or aromatase inhibitor therapy for breast cancer
• •19. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• •20. Patients who must take strong cytochrome cytochrome P450 (CYP3A) inhibitors such as clarithromycin, diltiazem, verapamil, itraconazole, or ketoconazole
• •21. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
• •22. Concurrent enrollment in another therapeutic clinical study