Cemiplimab Plus Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Inclusion criteria

• At least 18 years of age.
• Ability to understand the nature of this study, comply with study and follow-up procedures, and give written informed consent.
• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma. Primary tumor can be intact or post-resection with newly developed metastatic disease.
• Stage IV disease (measurable disease by Immunotherapeutics Response Evaluation Criteria in Solid Tumors is required).
• 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.
• One previous line of therapy for pancreatic ductal adenocarcinoma (NOT immunotherapy or cellular therapy).
• Last dose of chemotherapy administered \> 14 days prior to the initiation of study therapy.
• Last dose of radiation therapy or administered \> 28 days prior to the initiation of study therapy.
• Eastern Cooperative Oncology Group performance score of 0-1.
• 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.
• 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).
• Adequate renal function: Serum creatinine ≤ 1.5 times upper limit of normal.
• Calculated corrected QT Interval (QTcF) average of the triplicate electrocardiograms \<470 milliseconds.
• 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.
• 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

• Two or more lines of systemic or previous investigational therapy for metastatic pancreatic ductal adenocarcinoma.
• History of any autoimmune disease requiring treatment within the past 12 months prior to enrollment.
• History of transplanted organ/bone marrow.
• History of interstitial lung disease.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• History of previous malignancy (except in-situ cancer or basal or squamous cell skin cancer) within past 3 years prior to enrollment.
• History of immune checkpoint inhibitor therapy, ever.
• Known bleeding disorders (e.g., van Willebrand's disease or hemophilia).
• 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.
• Current use of a strong cytochrome P450 3A inhibitor (for example, antifungal medications, grapefruit juice, amiodarone, etc.).
• Presence of known central nervous system or brain metastases.
• 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.
• Life expectancy of \<3 months.
• Known active, not-controlled human immunodeficiency virus, hepatitis B or hepatitis C infection or diagnosis of immunodeficiency.
• Receipt of a live vaccine within 4 weeks of start of study medication.
• 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.
• 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.
• Pregnancy or lactation.
• Known allergic reactions to components of the study intervention, cemiplimab and/or gemcitabine.