LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

Primary Outcome Measure:

• Clinical benefit rate associated with LEE011 treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria will apply.

Secondary Outcome Measures:

• Overall Response (OR) of Partial Response (PR) or greater [ Time Frame: Baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ] [ Designated as safety issue: No ]
  Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply.
• Progression Free Survival (PFS) [ Time Frame: Every 8 weeks until death, assessed up to 24 months ] [ Designated as safety issue: No ]
  Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause
• Overall Survival (OS) [ Time Frame: Every 8 weeks until death, assessed up to 36 months ] [ Designated as safety issue: No ]
  Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause.
• Duration of Response (DOR) [ Time Frame: Baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ] [ Designated as safety issue: No ]
  Duration of response (DOR) is defined as time from the first documented response to the date first documented disease progression or relapse or death due to any cause.
• Safety and tolerability [ Time Frame: Baseline up to 30 days after last study treatment ] [ Designated as safety issue: Yes ]
  Safety and tolerability will be based on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g., electrocardiogram, vital signs) will be considered as appropriate.

Eligibility Criteria

Inclusion Criteria:

• Patient has a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative will be included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
• Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation
• Patient has received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
• Patient has progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

• Patients have received prior treatment with LEE011.
• Patient has clinically significant resting bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or QTcF > 450 msec.
• Patients has primary CNS tumor or CNS tumor involvement
• Patient has received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug