SARC041: Study of Abemaciclib Versus Placebo in Patients with Advanced Dedifferentiated Liposarcoma

Inclusion Criteria:

• Age ≥ 18 years

• Histologically confirmed diagnosis of dedifferentiated liposarcoma which is locallyrecurrent and/or metastatic. This study will accept the diagnosis made at theinvestigator's center.

• ECOG Performance Status of 0 or 1.

• At least one site of measurable disease on CT/MRI scan as defined by RECIST 1.1criteria. Baseline imaging must be performed within 28 days of Day 1 of study.

• Adequate organ function

• The patient can swallow oral medications.

• Patients who received radiotherapy must have completed and fully recovered from theacute effects of radiotherapy. A washout period of at least 14 days is requiredbetween end of radiotherapy and randomization.

• Patients who received chemotherapy must have recovered (Common Terminology Criteriafor Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy exceptfor residual alopecia or Grade 2 peripheral neuropathy prior to randomization. Awashout period of at least 21 days is required between last chemotherapy dose andrandomization (provided the patient did not receive radiotherapy).

• Written, voluntary informed consent

• Fertile men and women of childbearing potential must agree to use a highly effectivemethod of birth control during the treatment period and for 3 weeks after last studydrug administration in both sexes. Women of childbearing potential includepre-menopausal women and women within the first 2 years of the onset of menopause.Women of childbearing potential must have a negative pregnancy test ≤ seven days ofthe first dose of abemaciclib.

• Highly effective methods of birth control include an intrauterine device [IUD] orbarrier method. If condoms are used as a barrier method, a spermicidal agent shouldbe added as a double barrier protection.

• Measurable disease and evidence of progression of disease as defined by RECIST 1.1 (including newly diagnosed disease, new disease sites in a patient who waspreviously NED, or a 20% growth of existing lesions within 6 months ofregistration).

• Patients with central nervous system disease are eligible for enrollment if theyhave received prior radiotherapy or surgery within 3 months from completion oftherapy to sites of CNS metastatic disease and are without evidence of clinicalprogression.

Exclusion Criteria:

• Patients with documentation of well-differentiated liposarcoma only are specificallyexcluded, owing to its characteristically slow growth. If high grade areas aresuspected (dedifferentiation), but not proved by pathology analysis (e.g. afterprimary resection of a well-differentiated liposarcoma), a biopsy must be performedto demonstrate the high-grade dedifferentiated disease. If there is a questionregarding the diagnosis, the PI should be consulted.

• Patients with bulky disease who urgently need cytotoxic chemotherapy (likely withdoxorubicin + ifosfamide) will be excluded from this study. This is determined bythe treating physician. If there is a question regarding the appropriateness of thepatient for enrollment, the PI should be consulted.

• Prior systemic therapy with abemaciclib or any other selective CDK4 inhibitor (suchas palbociclib)

• Concurrent, clinically significant, active malignancies within 12 months of studyenrollment

• Patients with severe and/or uncontrolled concurrent medical disease that in theopinion of the investigator could cause unacceptable safety risks or compromisecompliance with the protocol

• Major surgery within 3 weeks prior to Day 1 of study or who have not recoveredadequately from prior surgery

• Patients with resectable for curative intent disease

• Patients that have GI absorption disorders that would impact the administration oforal abemaciclib.

• Women who are pregnant or nursing/breastfeeding.

• Known hypersensitivity to abemaciclib.

• Patients with untreated central nervous system disease.

• Inability to comply with protocol required procedures

• Patients currently taking the following drugs may interact with abemaciclib. Pleaserefer to Section 5.2 of protocol.

• 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.

• The patient has received an experimental treatment in a clinical trial within thelast 30 days or 5 half-lives, whichever is longer, prior to randomization, or iscurrently enrolled in any other type of medical research (for example: medicaldevice) judged by the sponsor not to be scientifically or medically compatible withthis study.