Abemaciclib in Combination With Androgen Deprivation Therapy for Locally Advanced Prostate Cancer

Inclusion Criteria: * Histologically confirmed (core biopsy proven) adenocarcinoma of prostate, localized high-risk or locally advanced. * One of the below: * Gleason 7-8, any T-stage, and PSA \> 20, * Gleason 8, ≥ T2, any PSA, * Gleason 9-10, any T-stage, any PSA * Available biopsy of primary tumor or resected tumor specimen with adequate samples. * Prior treatment with systemic anti-cancer agents is not allowed. * ECOG PS=0 or 1. * Must have at least 1 target lesion. * Adequate hematologic and end-organ function: * ANC ≥ 1500/mm3 * Platelet count ≥ 100,000/mm3 * Hb ≥ 9g/dl * Creatinine ≤ ULN or Creatinine Clearance (CrCl) ≥ 60 ml/min * Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who can have total Bilirubin \> 2.0 x ULN and direct bilirubin within normal limits are permitted). * AST, ALT and alkaline phosphatase ≤ ULN * Agreement to remain abstinent or use appropriate contraception. * Willingness and ability to consent for self to participate in study. * Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: * Prior treatment to CDK4-6 inhibitor. * Prior treatment with systemic agents or radiation treatment for the primary cancer. * Major surgical procedure or significant traumatic injury within 4 weeks prior to study treatment, and must have fully recovered from any such procedure. * Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. * Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment. * Known active viral or non-viral hepatitis or cirrhosis. * Any active infection requiring systemic treatment, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA). * Known history of AIDS (acquired immunodeficiency syndrome)-defining illness. * Patients must be surgically sterile or must agree to use effective contraception during the study treatment (including temporary breaks from treatment), and for at least 180 days after stopping last dose of Abemaciclib. * Other severe and/or uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that, in the judgment of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results and would make the patient inappropriate for this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea.) * Secondary malignancy requiring active treatment. Past history of malignancy other than prostate cancer treated with curative intent and not requiring additional treatment may be eligible after discussion with PI. * Patients with active autoimmune disease and history of inflammatory bowel disease. Brachytherapy boost will not be permitted.