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-Patients with a histologically or cytologically confirmed diagnosis of a solid tumor or lymphoma for which no further effective standard treatment is available
1) dose escalation phase: pRb-positive tumor tissue (immunohistochemical analysis)
2) dose expansion phase: tumors known to have aberrant activation of the D-cyclin-CDK4/6-INK4a-pRb pathway or whose tumors can be shown to harbor such an abnormality identified by IHC, by mutation analysis or by FISH. Patients with MCL, liposarcoma, HPVnegative HNSCC, melanoma, ER+ breast cancer and neuroblastoma are permitted to be enrolled in the study without documented pRb status.
A representative tumor specimen must be available for molecular testing. An archival tumor sample may be submitted; however, if one is not available, a newly obtained tumor biopsy specimen must be submitted instead.
- WHO performance status 0 or 1.
- Required baseline laboratory values:
o Absolute Neutrophil Count *1.5 x 109/L
o Hemoglobin * 9 g/dl <= 5.58 mmol/l
o Platelets * 100x109/L
o AST/SGOT and ALT/SGPT* 3 x Upper Limit of Normal (ULN) or * 5.0 x ULN if liver metastases are present
o Serum bilirubin * 1.5 x ULN
o Serum creatinine * 1.5 x ULN or 24-hour clearance * 50 ml/min.
o Potassium, magnesium and calcium within clinical relevant limits
- A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies and major surgery) and enrollment in this study, to allow the effects of prior therapy to have abated.
- Patients enrolled in the dose expansion phase must have at least one measurable lesion as defined by RECIST criteria for solid tumors or measurable nodal disease at baseline as defined by Cheson criteria for lymphoma.
- A negative serum pregnancy test * 72 hours before starting study treatment

Exclusion Criteria

- Patients with primary CNS tumors or brain metastases. However, if over a minimum of 3 months the disease is stable (confirmed by MRI) and if the patient remains asymptomatic, then the patient may be enrolled. Such patients must have no need for treatment with steroids or anti-epileptic medications.
-Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 and clinically significant gastroparesis, nausea, vomiting, or diarrhea of CTCAE grade > 1
- Autologous stem cell transplant within 3 months before the first dose of LEE011 or prior allogeneic stem cell transplant at any time
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
1) Left ventricular ejection fraction (LVEF) <45%
2) Complete left bundle branch block
3) Obligate use of a cardiac pacemaker or implantable cardioverter defibrillator
4) Congenital long QT syndrome or family history of unexpected sudden cardiac death
5) History or presence of ventricular tachyarrhythmia
6) Presence of unstable atrial fibrillation
7) Clinically significant resting bradycardia
8) QTcF >450 ms for males and >470 ms for females on screening ECG
9) Right bundle branch block and left anterior hemiblock (bifascicular block)
10) Acute MI or angina pectoris * 3 months prior to starting study drug
11) Other clinically significant heart disease
- The use of agents that are known to cause QTc prolongation
- Treatment with agents including vitamins, supplements, and herbal supplements that are either (i) metabolized solely through CYP3A4/5, CYP1A2 or BSEP and have a narrow therapeutic window or (ii) are strong inhibitors of CYP3A4/5, CYP1A2 or BSEP
- Concurrent severe and/or uncontrolled concurrent medical conditions e.g., uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection.
- Pregnant or lactating women.
- Women of childbearing potential and men with reproductive potential unwilling to use adequate contraception whilst on study therapy and for 3 months thereafter

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Frequency of Dose Limiting Toxicities.</p><br>

Secondary Outcome Measures

Name	Time	Method

Updated 7/22/2024

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