LEE011 Plus Everolimus in Patients With Metastatic Pancreatic Adenocarcinoma Refractory to Chemotherapy

Inclusion Criteria

• Histologically confirmed mPAC (mixed histology is acceptable as long as the predominant histology is pancreatic adenocarcinoma)
• Patient must consent to two mandatory biopsies and have tumor amenable to biopsy
• Measurable disease by RECIST v1.1 criteria (tumor ≥ 1 cm in longest diameter on axial image on CT or MRI and/or lymph node(s) ≥ 1.5 cm in short axis on CT or MRI) on baseline imaging
• Documented progression of disease on at least one 5-FU-based regimen and at least one GEM-based regimen for metastatic disease (progression during or within 3 months of the completion of adjuvant therapy is acceptable)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (see Table 2)
• Age ≥ 18 years
• Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intracranial disease
• Patients with available standard 12-lead ECG with the following parameters at screening (defined as the mean of the triplicate ECGs):
• QTcF interval at screening 1.5 - 3.0 x the upper normal limit of institution's normal range are acceptable as long as there is no persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia.
• Partial Thromboplastin Time (PTT) must be ≤ 1.5 × upper normal limit of institution's normal range and International Normalized Ratio (INR) 160 mmHg or <90 mmHg at screening
• Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug (see Table 4 for details):
• 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.