GVAX Pancreas Vaccine, Cyclophosphamide, Pembrolizumab, and Anti-CSF1R Monoclonal Antibody IMC-CS4 in Treating Patients with Resectable Pancreatic Adenocarcinoma

Inclusion Criteria

• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Patients with histologically or cytologically confirmed adenocarcinoma of the pancreas.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: A research core biopsy is required within 14 days prior to starting therapy. If a biopsy is attempted and unsuccessful, that patient still may be treated after review and approval of the principal investigator (PI) and investigational new drug (IND) sponsor.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Patients must have borderline resectable pancreatic adenocarcinoma at time of diagnosis as defined by National Comprehensive Cancer Network (NCCN) guidelines. Discussion will take place at multidisciplinary pancreatic tumor board.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Patients must not have metastatic disease.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Patients who received radiation therapy must have received last dose no longer than 28 days prior to enrollment.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Patients must have received last dose of chemotherapy at least 14 days or longer prior to receiving study related immunotherapy.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Lymphocytes >= 500 cells/mm^3.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Absolute neutrophil count >= 1,000 cells/mm^3.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Hemoglobin >= 9g/dL.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Platelets >= 100,000 cells/mm^3.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Serum creatinine within normal limits.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper limit of normal (ULN).
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Total bilirubin =< 1.5 x ULN * Subjects with Gilbert’s Syndrome should have direct bilirubin within normal institutional limits.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Female patient of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required to be shown as negative for the patient to be eligible.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: WOCBP must be willing to use an adequate method of contraception starting with visit 1 through 120 days after the last dose of study therapy. * Note: Complete abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. * Male subjects of childbearing potential must agree to use an adequate method of contraception starting with visit 1 through 120 days after the last dose of study therapy. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• ELIGIBILITY CRITERIA TO RECEIVE NEOADJUVANT STUDY TREATMENT: Ability to understand and the willingness to sign a written informed consent document.
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Patients must have had surgical resection of primary tumor (R0, R1 and R2 resections).
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Patients must not have evidence of metastatic disease by imaging or disease progression by imaging as per immune-Related Response Criteria (irRC).
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: If no adjuvant chemotherapy was given, patient must have had surgery within 90 days prior to planned day 1 of adjuvant study immunotherapy. If adjuvant chemotherapy was given patients must have had surgery within 180 days of adjuvant study immunotherapy.
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: ECOG performance status 0-1.
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Lymphocytes >= 500 cells/mm^3
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Absolute neutrophil count >= 1,000 cells/mm^3
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Hemoglobin >= 9 g/dL
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Platelets >= 100,000 cells/mm^3
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Serum creatinine within normal limits
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: AST and ALT =< 2 x ULN
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Total bilirubin =< 1.5 x ULN * Subjects with Gilbert’s Syndrome should have direct bilirubin within normal institutional limits
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Female patient of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required to be shown as negative for the patient to be eligible.
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: WOCBP must be willing to use an adequate method of contraception starting with Visit 1 through 120 days after the last dose of study therapy. * Note: Complete abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. * Male subjects of childbearing potential must agree to use an adequate method of contraception starting with visit 1 through 120 days after the last dose of study therapy. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• ELIGIBILITY CRITERIA TO RECEIVE ADJUVANT STUDY TREATMENT: Ability to understand and the willingness to sign a written informed consent document.
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Patients must not have metastatic disease by interval study imaging or disease progression by interval study imaging as per irRC done.
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: ECOG performance status 0-1.
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Lymphocytes >= 500 cells/mm^3
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Absolute neutrophil count >= 1,000 cells/mm^3
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Hemoglobin >= 9 g/dL
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Platelets >= 100,000 cells/mm^3
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Serum creatinine =< 1.5 x ULN * If the serum creatinine is > 1.5 x ULN, but the estimated glomerular filtration rate (GFR) is > 30 mL/min, then the booster therapy can be administered.
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: AST and ALT =< 2 x upper limit of normal (ULN)
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Total bilirubin =< 1.5 x ULN * Subjects with Gilbert’s Syndrome should have direct bilirubin within normal institutional limits
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Female patient of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required to be shown as negative for the patient to be eligible.
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: WOCBP must be willing to use an adequate method of contraception starting with Visit 1 through 120 days after the last dose of study therapy. * Note: Complete abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. * Male subjects of childbearing potential must agree to use an adequate method of contraception starting with visit 1 through 120 days after the last dose of study therapy. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• ELIGIBILITY CRITERIA TO RECEIVE BOOSTER THERAPY: Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Patient is currently participating or has participated in a study of an investigational agent within 28 days of cycle 1 day 1 (C1D1) of this study or is currently using an investigational device.
• Patients who have had surgery 28 days prior to first dose of the study drug excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
• Patients must not have received systemic steroids, immunosuppressant medications and anti-neoplastic treatment in the past 14 days.
• Patients with a history of prior treatment with immunotherapy agents (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies)
• Patients receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration. Use of such agents while on study is also prohibited during immunotherapy treatment.
• Patients who have received any prophylactic vaccine within 14 days of first dose of study drug or received a live vaccine within 30 days of planned start of study therapy.
• Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of any autoimmune disease, including any history of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, as well as history of symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener’s granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis). Patients with thyroid disease will be allowed. Autoimmune diagnoses not listed here must be approved by the principal investigator.
• Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
• Has history of (non-infectious) pneumonitis that required steroids, history or evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has a pulse oximetry < 92% on room air.
• Evidence of ascites on imaging at study enrollment (allowed post-surgery during administration of adjuvant and booster therapy).
• Requires the use of home oxygen.
• Has a known history of human immunodeficiency virus (HIV) (HIV1/2 antibodies), hepatitis B, or hepatitis C infection (patients who are hepatitis C antibody positive may be enrolled if they are confirmed with negative viral load at screening).
• Any concurrent malignancy or myeloproliferative disorder whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this study’s investigational drug. Patients with a previous non-pancreatic, nonperiampullary malignancy without evidence of disease for > 5 years will be allowed to enter the trial.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to investigational product administration.
• Women of child bearing potential or sexually active fertile men with partners who are women of child bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 120 days after the last dose of investigational product.
• Patient is unwilling or unable to follow the study schedule for any reason.