Phase I Trial of LCL161 and Gemcitabine Plus Nab-Paclitaxel in Metastatic Pancreatic Cancer

Inclusion Criteria: 1. Patients must provide written informed consent prior to any screening procedures. 2. A signed Patient Authorization Form (HIPPA) has been obtained prior to registration. 3. Age 18 years or older. 4. Willing and able to comply with scheduled visits, treatment plan and laboratory tests 5. Patient is able to swallow and retain oral medication. 6. Histologically or cytologically documented measureable metastatic (Stage IV) pancreatic cancer with disease by computed tomography scan as defined by RECIST Version 1.1. 7. ECOG performance status 0-1. 8. Required baseline laboratory status: * Hemoglobin (Hgb) ≥ 90 g/L (9 g/dL) * Platelets ≥ 100 x 109/L (100,000/mm3) * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/mm3) * Serum total bilirubin ≤ 1.5 x ULN (upper limit of normal) * AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN, except for patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN * Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 40 mL/min 9. Patient did not receive previous treatment for Stage IV pancreatic cancer. Note: However, prior adjuvant treatment with fluorouracil or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If patient received adjuvant therapy, tumor recurrence must have occurred ≥ 6 months after the last treatment. Exclusion Criteria: 1. Patient has any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while on the study or that could confound discrimination between disease- and study treatment-related toxicities. 2. Patient has impaired cardiac function or clinically significant cardiac diseases, including any of the following: * History or presence of ventricular tachyarrhythmia * Presence of unstable atrial fibrillation (ventricular response \> 100 bpm); Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria 3. Patient is currently receiving chronic (\> 14 days) treatment with corticosteroids at a dose ≥ 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug. 4. Patient is currently receiving treatment with agents that are metabolized solely through CYP3A4/5 and have a narrow therapeutic index or are strong CYP2C8 inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates. Caution should be used in patients taking other CYP2C8- or CYP3A4/5-interacting agents. 5. Patient has impairment of Gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LCL161. 6. Patient is a pregnant or breast feeding (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive β-HCG laboratory test (\> 5 mIU/mL). 7. Patient is a woman of child-bearing potential, defined as all women physiologically capable of becoming pregnant and refusing to use highly effective methods of contraception during dosing and for 90 days after study treatment. Highly effective contraception methods include: * Total abstinence or * Male partner or female sterilization or * Combination of any 2 of the following (a+b or a+c, or b+c): 1. Use of oral, injected, or implanted hormonal methods of contraception 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 3. Barrier methods of contraception: condom for male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal form/gel/film/cream/ vaginal suppository. Note: Postmenopausal women are allowed to participate in this study. Women are considered postmenopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks earlier. In the case of oophorectomy alone, a woman is considered to be not of child bearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment. 8. Patient is abstaining from using a condom. Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. 9. Patient has a history of lymphoma with or without treatment. 10. Patient has a history of interstitial pneumonitis.