A Study of LEE011 With Everolimus in Patients With Advanced Neuroendocrine Tumors

Inclusion Criteria

• Patient has signed the Informed Consent prior to any screening procedures being performed and is able to comply with the protocol requirements.
• Adults ≥ 18 years old
• Histologic or cytologic diagnosis of a WDNET, Ki67 ≤ 30%, unresectable, of foregut origin (thymic, bronchopulmonary, gastric, duodenal, and pancreatic) confirmed by the enrolling institution

*Note: If patients have a functional NET, they are permitted to continue on a somatostatin analog for hormonal symptom control

• MSK patient has tissue available from a previous biopsy for the evaluation of potential predictive biomarkers. If tissue is not available for MSK patient, a new tumor specimen will need to be obtained prior to the start of study treatment If archived tissue is available, participating site patient will provide for the evaluation of potential predictive biomarkers. If tissue is not available for participating site patient, a new tumor specimen is optional prior to the start of study treatment.
• Documented radiological evidence for disease progression (measurable or nonmeasurable) ≤12 months prior to enrollment
• Disease that is currently not amenable to surgical resection with curative intent as determined by the treating investigator
• Measurable disease as defined by RECIST v1.1
• ECOG performance status 0 or 1 or KPS performance status 100 to 70
• Patient has adequate bone marrow and organ function as defined by the following laboratory values at screening:
• Absolute neutrophil count ≥1.5 x 10^9/L
• Platelets ≥ 100 x 10^9/L
• Hemoglobin ≥ 9.0 g/dL
• INR ≤ 1.5
• Serum creatinine 8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
• Documented cardiomyopathy
• Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
• Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting study drug)
• Inability to determine the QTcF interval
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
• Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug
• Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges, that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
• Herbal preparations/medications, dietary supplements
• Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment

°The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)

• Participation in a prior investigational study within 30 days prior to