Abemaciclib in Treating Patients with Advanced Solid Tumors with CCND1/2/3 and CDK4/6 Genetic Alterations

Inclusion Criteria

• Participants must have a histologically or cytologically confirmed advanced solid tumor of a non-breast origin, for which standard therapy proven to provide clinical benefit does not exist or is no longer effective
• For enrollment to arm 1: participants must have a confirmed CCND1, 2, or 3 amplification, CCND1 mutation, or a CCND1 splice variant expected to lead to nuclear retention of cyclin D1 protein, via Dana-Farber Cancer Institute (DFCI)/Brigham and Women's Hospital (BWH) OncoPanel or any Clinical Laboratory Improvement Act (CLIA)-certified method
• For enrollment to arm 2: participants must have a confirmed CDK4 or CDK6 amplification, identified via DFCI/BWH OncoPanel or any CLIA-certified method
• Participants must have evaluable or measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count >= 1.5 x 10^9 /L
• Platelets >= 100 x 10^9/L
• Hemoglobin >= 8 g/dL * Note: 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
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) * Note: Patients with Gilbert’s syndrome with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal limits are permitted
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN
• The effects of abemaciclib on the developing human fetus are unknown; for this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months after completion of abemaciclib administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a negative serum pregnancy test is required for women of childbearing potential prior to study entry
• Ability to understand and the willingness to sign a written informed consent document
• Ability to swallow and retain oral medication

Exclusion Criteria

• Participants who have had chemotherapy, biologic therapy, investigational agents, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Participants 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
• Participants who received 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
• The participant has had major surgery within 14 days prior to randomization
• Participants who have had oral targeted therapy or oral tyrosine kinase inhibitors (TKIs) within 5 half-lives prior to entering the study
• Participants who have received prior treatment with a CDK4/6 inhibitor
• Participants must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study
• Participants who have received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomization, or are currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study
• Participants with hematologic lymphoma
• Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable and/or require radiation therapy are excluded; * Participants with brain metastases that do not meet the above criteria in the opinion of the treating investigator * Symptomatic disease is allowed as long as symptoms are controlled and stable
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib
• The participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgement of the investigator, would preclude participation in 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)
• Pregnant women are excluded from this study because abemaciclib is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with abemaciclib, breastfeeding should be discontinued if the mother is treated with abemaciclib. A negative serum pregnancy test is required for women of childbearing potential prior to study entry
• Participants with known human immunodeficiency virus (HIV)-positive status are ineligible because these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
• The participant has active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]). Screening is not required for enrollment
• Participants receiving an enzyme-inducing antiepileptic drug (EIAED) who cannot be transferred to a non-EIAED (e.g., levetiracetam, lacosamide, lamotrigine, etc.) prior to the initiation of protocol therapy
• The patient has serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, 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)
• The patient has a 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