Personalized Vaccine With SOC Chemo Followed by Nivo in Pancreatic Cancer

This is a single center, single arm, phase Ib trial to evaluate the feasibility, safety, immunogenicity, and efficacy of subcutaneous dendritic cell (DC) vaccine loaded with personalized peptides \[PEP-DC vaccine\] in combination with standard of care adjuvant chemotherapy (subgroup 1: mFOLFIRINOX or subgroup 2: gemcitabine and capecitabine), followed by the antibody nivolumab in patients with non-metastatic surgically resected pancreatic adenocarcinoma. All patients will have previously undergone collection of resected advanced pancreatic tumor tissue under a different research protocol with a separate informed consent. After registration, all patients will receive standard of care chemotherapy: Subgroup 1: intravenous mFOLFIRINOX for twelve 2-week cycles. Subgroup 2: intravenous gemcitabine, and oral capecitabine for eight 21-day cycles. Additionally, all eligible patients will undergo apheresis during the cycle 5 of mFOLFIRINOX (subgroup 1) or the last week of cycle 3 of gemcitabine/ capecitabine (subgroup 2) to collect peripheral blood mononuclear cells (PBMCs) for dendritic cell vaccine production. All patients will receive at least six PEP-DC vaccinations starting concomitant with the 8th cycle (subgroup 1) or the 5th cycle (subgroup 2) of chemotherapy. Subgroup 1: Vaccine will be delivered subcutaneously every 4 weeks, on day 3(+1) of every second 14-day cycle, and thereafter every four weeks starting from the first nivolumab administration. Subgroup 2: Vaccine will be administered subcutaneously every 3 weeks, on day 9 (the day after last gemcitabine infusion) of each 21-day cycle, and thereafter every four weeks starting from the second nivolumab administration. Nivolumab will be administered intravenously over a period of 30 minutes to all patients, for a maximum duration of 2 years, as follows: Subgroup 1: Nivolumab treatment will start after the last cycle of chemotherapy (2 weeks after C12D1) and will be given as flat dose of 240 mg given every 2 weeks, during 14 weeks (2-week cycles). Then it will be administered as flat dose of 480 mg every 4 weeks (4-week-cycles), until the last vaccine dose. Subgroup 2: Nivolumab treatment will start after the last cycle of chemotherapy (3 weeks after C8D1) as flat dose of 240 mg given every 2 weeks, for 14 weeks. Then it will be administered as flat dose of 480 mg every 4 weeks, until the last vaccine dose. Nivolumab treatment should be maintained for at least for 8 weeks after end of the last chemotherapy cycle if vaccination stops earlier. Nivolumab maintenance for both subgroups: After the end of combined treatment period (vaccination plus nivolumab), nivolumab will be given at 480 mg (flat dose) every four weeks to all patients until appearance of new lesions, unacceptable toxicity or until the maximum time for nivolumab treatment (2 year) is reached. Regular physical examination, radiological evaluation and blood testing for safety parameters will be performed according to the schedule during treatment.