BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer

Inclusion Criteria: * Histologically or cytologically confirmed newly diagnosed treatment-naïve metastatic adenocarcinoma of the pancreas with metastatic disease diagnosed no more than 6 weeks prior to enrollment. Patients with advanced pancreatic cancer progressed on 5-FU (or capecitabine) based regimen will be allowed in the expansion cohort. * Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam. * At least 18 years of age. * Life expectancy \> 3 months. * ECOG performance status ≤ 1 * Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Hemoglobin ≥ 9.0 g/dL * Total bilirubin ≤ IULN * AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN * Creatinine ≤ 1.5 x IULN OR GFR of ≥ 50 mL/min * Cardiac function ≥ ILLN, e.g., LVEF of \> 50% as assessed by MUGA or ECHO, QTc \< 470 ms * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for three months following study discontinuation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: * Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment. * A history of other malignancy with the exception of those treated with curative intent with no evidence of disease for 2 years. * Currently receiving any other investigational agents. * Known brain metastases or CNS involvement. * Significant ascites that require therapeutic paracentesis. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BVD-523, gemcitabine, nab-paclitaxel, or other agents used in the study. * Neuropathy ≥ grade 2. * History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR). * History of interstitial lung disease or pneumonitis. * Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, and CYP3A4, or strong inducers of CYP3A4 (see Appendix B). * Gastrointestinal condition which could impair absorption of BVD-523 or inability to ingest BVD-523. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry. * Known HIV-positivity.