GI-4000 With Adoptive Transfer in Pancreatic Cancer

This Phase I/Pilot study will assess the safety and feasibility of the GI-4000 series vaccine with or without adoptive T cell transfer in subjects with locally advanced pancreatic cancer undergoing chemotherapy, radiotherapy, and surgical resection. Subjects will be randomized to either ARM A (GI-4000vaccine) or ARM B (GI-4000 vaccine and activated T cell transfer). All subjects will undergo apheresis of mononuclear cells immediately before receiving four cycles of gemcitabine/oxaliplatin (GemOx) chemotherapy ("immune preservation phase"). After the completion of chemotherapy, the apheresis product will be reinfused, and the subjects will enter the "priming phase," in which two biweekly doses (dose #1 and #2) of the appropriate GI-4000 vaccine (the one that best matches the mutations found in the patient's tumor) and a single dose of the Prevnar pneumococcal conjugate vaccine will be administered. At this time, those subjects who have not developed distant metastatic disease by CT/MRI will undergo chemoradiation, with ARM B subjects receiving a second apheresis immediately prior to the initiation of the chemoradiation. The pheresed product will be activated and expanded ex vivo and reinfused after chemoradiation is completed. All subjects will receive two more biweekly boosts of the GI-4000 vaccine (doses #3 and #4) while undergoing restaging with CT/MRI ("boosting phase"). Those who have not developed metastatic disease will undergo surgical evaluation for tumor resection. Patients who undergo R0 or R1 resection will receive up to three more weekly doses of GI-4000 prior to the initiation of adjuvant gemcitabine, monthly doses of GI-4000 during the four cycles of gemcitabine chemotherapy, and monthly GI-4000 doses thereafter. At the end of gemcitabine chemotherapy, apheresis will be performed for endpoint correlative studies. Those who are not candidates for surgery or whose tumors are not completely resected will continue to receive GI-4000 monthly booster vaccination.