Background: Surgical resection is the only potentially curative treatment for pancreatic adenocarcinoma (PDAC) but involvement of adjacent vital structures in locally advanced pancreatic adenocarcinoma (LAPC) precludes upfront resection. Neoadjuvant chemotherapy and/or radiation allows some LAPC patients to undergo resection but outcomes remain dismal. In this trial, we investigate the benefit of combining chemotherapy, radiation, and immunotherapy to improve outcomes in LAPC by enhancing antitumor immunity. The use of GVAX, Nivolumab, and BMS-813160 is hypothesized to promote immune responses through enhanced effector T cell infiltration and activation by GVAX and nivolumab while inhibiting immunosuppressive tumor associated macrophages via CCR2/5 inhibition with BMS-813160. Testing this combination in LAPC will facilitate assessment of the changes this combination produces in the tumor microenvironment. Methods: This open-label, single center two-arm phase I/II trial uses neoadjuvant/adjuvant nivolumab and BMS-813160 +/- GVAX following 8 to 16 doses of FOLFIRINOX and SBRT in patients with newly diagnosed LAPC. The primary endpoint of the phase I portion is safety of nivolumab, BMS-813160, and GVAX in patients with LAPC following chemotherapy and SBRT. The phase II portion randomizes patients 1:1 to nivolumab and BMS-813160 +/- GVAX with primary endpoint of immune response defined as > 80% increase in CD8+CD137+ cell infiltration. For the phase I portion a 3+3 dose escalation was used: nivolumab 480mg IV and GVAX 5x10⁸ cells intradermal were administered at a fixed dose every 4 weeks. BMS-813160 was administered at a dose of 150mg and 300mg PO BID in levels 1 and 2 respectively. DLTs were evaluated during the 1^st cycle of treatment and study-related adverse events (AE) were graded according to NCI CTCAE v5.0. Results: In the phase I portion of this trial, 13 patients were enrolled. The patient characteristics of the enrolled patients were: median age (range), 67 (44, 78), Female/Male, (4/9), Race, (Asian: 2, Black: 3, White: 8), histological grade (moderately/poor/moderately poor), (10/2/1). Nine of the 13 patients proceeded to immunotherapy after neoadjuvant chemotherapy and radiation. Three patients received treatment at dose level 1 and 6 patients at dose level 2. No DLTs were observed with the only grade 3 or higher AE being maculo-papular rash (n = 1). The RP2D for BMS-813160 was determined to be 300mg PO BID. Conclusions: We determined that nivolumab 480mg IV q4 weeks, GVAX 5x10⁸ cells intradermal q4 weeks, and BMS-813160 300mg PO BID were the RP2D for the phase 2 portion of this investigation which is ongoing. This combination appears safe and neoadjuvant use does not lead to delay in surgery. Clinical trial information: NCT03767582.