Inclusion Criteria:
1. At least 18 years of age.
2. Ability to understand the nature of this study, comply with study and follow-up procedures, and give written informed consent.
3. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma. Primary tumor can be intact or post-resection with newly developed metastatic disease.
4. Stage IV disease (measurable disease by Immunotherapeutics Response Evaluation Criteria in Solid Tumors is required).
5. Alterations in SWI/SNF complex chromatin remodeling genes (ARID1A, ARID1B, PBRM1, SMARCA4 and SMARCB1, etc.) detected by next generation sequencing performed prior to enrollment on an ultrasound-guided core biopsy of the primary tumor.
6. One previous line of therapy for pancreatic ductal adenocarcinoma (NOT immunotherapy or cellular therapy).
7. Last dose of chemotherapy administered \> 14 days prior to the initiation of study therapy.
8. Last dose of radiation therapy or administered \> 28 days prior to the initiation of study therapy.
9. Eastern Cooperative Oncology Group performance score of 0-1.
10. Adequate bone marrow function: Absolute neutrophil count ≥ 1,500 cells per microliter; Platelet count ≥ 100,000 cells per microliter; Hemoglobin ≥ 9.0 grams per deciliter.
11. Adequate hepatic function: Total bilirubin ≤ 1.5 times upper limit of normal (NOTE high bilirubin levels due to Gilbert's syndrome are allowed); Aspartate transaminase ≤ 3.0 times upper limit of normal (≤5.0 times upper limit of normal if liver metastases are present); Alanine transaminase ≤ 3.0 times upper limit of normal (≤5.0 times upper limit of normal if liver metastases are present).
12. Adequate renal function: Serum creatinine ≤ 1.5 times upper limit of normal.
13. Calculated corrected QT Interval (QTcF) average of the triplicate electrocardiograms \<470 milliseconds.
14. Participants not of child-bearing potential, or participants of child-bearing potential who agree to use adequate contraceptive measures during the study and for at least 6 months after the last cemiplimab dose; who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to initiation of study therapy.
15. For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner during study participation and for at least 6 months after the last cemiplimab dose.
Exclusion Criteria:
1. Two or more lines of systemic or previous investigational therapy for metastatic pancreatic ductal adenocarcinoma.
2. History of any autoimmune disease requiring treatment within the past 12 months prior to enrollment.
3. History of transplanted organ/bone marrow.
4. History of interstitial lung disease.
5. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
6. History of previous malignancy (except in-situ cancer or basal or squamous cell skin cancer) within past 3 years prior to enrollment.
7. History of immune checkpoint inhibitor therapy, ever.
8. Known bleeding disorders (e.g., van Willebrand's disease or hemophilia).
9. Current use of warfarin or other vitamin K antagonists. NOTE: if therapeutic anticoagulation is necessary, low molecular weight heparin or oral factor Xa inhibitors are the anticoagulants of choice.
10. Current use of a strong cytochrome P450 3A inhibitor (for example, antifungal medications, grapefruit juice, amiodarone, etc.).
11. Presence of known central nervous system or brain metastases.
12. History of other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study.
13. Life expectancy of \<3 months.
14. Known active, not-controlled human immunodeficiency virus, hepatitis B or hepatitis C infection or diagnosis of immunodeficiency.
15. Receipt of a live vaccine within 4 weeks of start of study medication.
16. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment.
17. Major surgery within 4 weeks of the start of study treatment. Major surgeries are defined as those surgeries that require general anesthesia. Insertion of a vascular access device, biliary drainage tube, gastrointestinal stent are NOT considered major surgery.
18. Pregnancy or lactation.
19. Known allergic reactions to components of the study intervention, cemiplimab and/or gemcitabine.
