trial of neoadjuvant and adjuvant nivolumab and bms-813160 with or without gvax for locally advanced pancreatic ductal adenocarcinomas.

Conditions: Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC); Pancreatic Ductal Adenocarcinoma

Summary: the purpose of this study is to evaluate if the combination of nivolumab and a ccr2/ccr5 dual antagonist (bms-813160) with gvax is safe in patients with locally advanced pancreatic cancer (lapc) who have received chemotherapy and radiotherapy, and to see if this combination therapy enhances the infiltration of cd8+cd137+ cells in pdacs .


Eligibility criteria:
inclusion criteria: * age ≥18 years. * patients with histologically- or cytologically-proven, surgically unresectable, locally advanced pancreatic adenocarcinoma. * if the patient does not have a diagnostic biopsy that is adequate for review at our institution, the patient must agree to a research core biopsy to be performed at johns hopkins. * if the patient's available imaging is not adequate for review by our institution, the patient must agree to a repeat imaging to be performed at johns hopkins. * patients cannot have had any prior therapy for the locally advanced pancreatic adenocarcinoma. * ecog performance status 0 or 1 * life expectancy greater than 3 months. * able to swallow pills or capsules. * patient must have adequate organ function defined by the study-specified laboratory tests. * patients must be eligible to receive folfirinox-based chemotherapy. * patients must be willing to be treated with stereotactic body radiation therapy (sbrt) only at johns hopkins hospital. * patients must be willing to undergo a core biopsy of the pancreatic cancer. * patients must be willing to undergo a biopsy of the pancreatic cancer if the patient is not deemed a surgical candidate during the pre-surgical evaluation. * must use acceptable form of birth control while on study. * ability to understand and willingness to sign a written informed consent document. exclusion criteria: * have had non-folfirinox-based chemotherapy for the pancreatic cancer. * have received any anti-neoplastic biologics, vaccines or hormonal treatment, including investigational drugs, within 28 days of the first dose of study. * history of past treatment with immunotherapy agents prior to initial enrollment into this study (including, but not limited to: il-2, interferon, anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, anti-ox-40, anti-cd40, anti-ctla-4 or anti-ccr2/5 drugs). * have had prior organ or tissue allograft or allogeneic bone marrow transplantation, including corneal transplants. * is currently participating or has participated in a study of an investigational agent or using an investigational device for the treatment of cancer. * current use of immunosuppressive medications within 14 days prior to study medications. * have received any vaccine within 14 days prior to study medications. * receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (g-csf), gm-csf, erythropoietin, within 14 days of the first dose of study medication. * history of any autoimmune disease. patients with thyroid disease will be allowed. * has a history of (non-infectious) pneumonitis or current pneumonitis. * has a pulse oximetry \< 92% on room air. * requires the use of home oxygen. * patients with uncontrolled intercurrent illness including, but not limited to, myocardial infarction or stroke/transient ischemic attack within the past 6 months, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * 12-lead electrocardiogram with qrs ≥ 120 msec, except right bundle branch block ; qtcf (qt corrected for heart rate using fridericia's method) ≥ 480 msec, except right bundle branch block * has an active infection requiring systemic therapy. * infection with hiv or hepatitis b or c. * any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, early stage prostate cancer, or carcinoma in situ of the cervix. * current or recent (within 3 months of study treatment administration) gastrointestinal disease that could impact the absorption of study treatment. * any gastrointestinal surgery that is likely impact upon the absorption of study treatment. * inability to tolerate oral medication. * unable to have blood drawn. * have had surgery within 28 days of the first dose of study medication. * prior use of strong/moderate cyp3a4 inhibitors or inducers within 28 days of the first dose of bms-813160. * prior use of class i antiarrhythmics within 28 days of first dose of study medication. * has ascites requiring medical management. * presence of duodenal or gastric invasion by the tumor. * hypersensitivity reaction to any monoclonal antibody. * known allergy or hypersensitivity to study drugs or any of their components of the study arm that participant is enrolling. * woman who are pregnant or breastfeeding. * patient is unwilling or unable to follow the study schedule for any reason.

Keywords: gvax nivolumab ccr2/ccr5 dual antagonist anti-pd-1 cancer vaccine monoclonal antibody checkpoint inhibitor myeloid modulating agent immunotherapy neoadjuvant chemotherapy stereotactic body radiation therapy sbrt pancreatic cancer pancreatic ductal adenocarcinoma pdac locally advanced pancreatic ductal adenocarcinoma lapc