BrafPanc: A Phase II Trial of Binimetinib in Combination With Encorafenib in Patients With Pancreatic Malignancies and a Somatic BRAFV600E Mutation

• 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

• REGISTRATION: 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)

• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 14 days prior to registration)

• Platelet count \>= 75,000/mm\^3 (obtained =\< 14 days prior to registration)

• Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to registration)

• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration)

• Aspartate transaminase (AST) =\< 2.5 x ULN; in participants with liver metastases =\< 5 x ULN (obtained =\< 14 days prior to registration)

• Aminotransferase (ALT) =\< 2.5 x ULN; in participants with liver metastases =\< 5 x ULN (obtained =\< 14 days prior to registration)

• Calculated creatinine clearance must be \>= 45 ml/min using the Cockcroft Gault formula (obtained =\< 14 days prior to registration)

• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only

• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study). Note: During the active monitoring phase of a study (i.e., active treatment), participants must be willing to return to the consenting institution for follow-up

• Ability to swallow the investigational product tablets and capsules

• Willing to provide tissue and blood samples for correlative research purposes