Patient description: The patient is a 57-year-old man with abdominal pain and vomiting. The pain started gradually about 20 hours ago in the epigastric and periumbilical regions, radiating to his back. He drinks around 60 units of alcohol per week and smokes 22 cigarettes per day. He is healthy with no history of allergies or using any medications. His family history is positive for type 2 diabetes (his father and sister). He lives alone and has no children. The abdomen is tender and soft. His bowel sounds are normal. His heart rate is 115/min and blood pressure 110/75 mmHg. The lab results are remarkable for leukocytosis (19.5), urea of 8.5, high CRP (145), high amylase (1200) and Glc level of 15. Cross-sectional imaging was negative for obstructive pancreatitis.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Locally Advanced Pancreatic Carcinoma Metastatic Pancreatic Carcinoma Recurrent Pancreatic Carcinoma Stage III Pancreatic Cancer AJCC v8 Stage IV Pancreatic Cancer AJCC v8 PRE-REGISTRATION Histological confirmation of a pancreatic malignancy as confirmed by the local pathology lab Patients whose disease has progressed on (or who were intolerant of) at least one line of therapy for metastatic disease Patients whose disease has recurred with metastatic disease =< 12 weeks of completion of neoadjuvant or adjuvant systemic chemotherapy; or patients with locally advanced disease whose disease progressed to metastatic disease on, or =< 12 weeks after completion of systemic chemotherapy would also be eligible Provide informed written consent =< 28 days prior to pre-registration Central electronic/paper confirmation of the presence of a BRAF V600E mutation. This review is mandatory prior to pre-registration to confirm eligibility. Results from a Clinical Laboratory Improvement Act (CLIA)/College of American Pathologists (CAP) certified testing lab (commercial or institutional) that confirm the presence of a BRAF V600E mutation in the patient's tumor must be submitted for central review NOTE: Registration must occur =< 30 days after pre-registration Confirmation of the presence of BRAF V600E mutation in the patient's tumor Measurable disease Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2. (Form is available on the Academic and Community Cancer Research United [ACCRU] web site)  Patients whose tumor harbors a BRAF non-V600E mutation or a BRAF fusion Prior therapy with BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib) Known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception NOTE: Female participants of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, and to not donate ova from screening until 30 days after the last dose of study drug NOTE: Male participants must agree to use methods of contraception that are highly effective or acceptable, and to not donate sperm from screening until 90 days after the last dose of study drug Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens