The purpose of this study is to determine whether ribociclib are effective and safe in the treatment of progressive well/dedifferentiated liposarcoma (WDL/DDL).

The expected duration of this study is 36 months (24 months accrual period and 12 month follow up period). Enrollment into the screening or treatment phase of the study will be stopped when the actual subject numbers have been achieved.

This single arm single institution, open label, prospective, phase II trial will evaluate the efficacy and safety of oral 600mg/daily in 28 day cycles of ribociclib in advanced well-differentiated liposarcoma (WDL) and de-differentiated liposarcoma (DDL) patients. Number of patients in the study will reflect the reconciliation between statistical requirements and incidence.

Treatment will continue until disease progression, development of unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision.

All screening requirements must be completed within 28 days of the visit (except for CDK4/6 amplification and pRb, p16 and cyclin D staining status which may be completed in advance). Patients will be examined on cycle 1 day-1 and every 2 weeks, including complete blood count (CBC) and chemistry, for the first 8 weeks of treatment, and thereafter every month until disease progression. CT/MRI imaging (contrast) will be performed every 8 weeks for response evaluation. Clinical benefit as well as individual categories of response (complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) will be determined using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST). Response duration endpoints, including PFS, PFS at 12 weeks and OS will be assessed using the Kaplan-Meier method. Toxicity (AEs) will be recorded using the NCI- Common Toxicity Criteria for Adverse Effects v 4.03 (NCI-CTCAE). Screening procedures will include quantitative analysis of CDK4 gene copy number using FISH, immunostaining for p16 and cyclin D1 all using formalin fixed paraffin embedded (FFPE) tissue sections. In addition tumor DNA, extracted from FFPE tissue (after choosing optimal area by a Pathologist), will be submitted to a next generation sequencing analysis ("ion ampliseq" cancer panel v2©) for a later exploratory analysis.

Inclusion Criteria:

1. Written informed consent
2. Age ≥ 18 years
3. Histological confirmed diagnosis of WDL/DDL with metastatic or locally advanced disease not amenable to complete resection.
4. WDL/DDL patients must have documentation of disease progression within 6 months prior to study entry.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Measurable disease by RECIST v1.1 criteria. At least one measurable lesion located outside of a previously irradiated area.
7. Formalin fixed paraffin embedded tumor blocs and representative hematoxylin/eosin slides (preferably both) should be provided for immunohistochemistry staining and molecular analysis of 50 gene signature panel and must have increased CDK4 gene copy number (at least >/=3) and proficient Rb gene.
8. Patient has adequate bone marrow and organ function.
9. Must be able to swallow ribociclib capsules/tablets.

Exclusion Criteria:

1. A known hypersensitivity to ribociclib or any of its excipients.
2. A concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
3. Patients with central nervous system (CNS) involvement at least 4 weeks from prior therapy completion
4. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening)
5. On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >450 msec
6. Participation in a prior investigational study within 30 days prior to enrollment
7. Patient has had major surgery within 14 days prior to starting study drug