Howeve r, for tables by time point the percentages will be calculated using the number of patients with available data at that time point . 3 STUDY OBJECTIVES AND DESIGN 3.1 Study Objectives The primary objectives of the study are: • To assess the safety of GM -CSF/TG01 vaccination and adjuvant chemotherapy. • To assess the immune response to GM -CSF/TG01 and the effect of adjuvant chemotherapy in patient s receiving GM -CSF/TG01 after primary resection of pancreatic adenocarcinoma. The secondary objective of this study is: • To assess at 2 years the clinical efficacy of GM -CSF/TG01 in patient s with resected pancreatic cancer. The exploratory objectives of the study are: Syne qua non study no: TAX12001 Targovax ASA study no: CT TG01 -01 Date: 02MAY2018 Page 6 of 21 Version: Amendment 1.0 Final 1.0 ST/form/010/10 • To assess the relationship of Kirsten rat sarcoma viral oncogene homolog ( KRAS ) status to recurrence. • Monitor CA19- 9 levels . 3.2 Study Design This is a Phase I /II trial of TG01 and gemcitabine as adjuvant therapy for testing patient s with resected adenocarcinoma of the pancreas . Patients will be enrolled in 5 study centre(s) and the study duration will be approximately 5 years. Phase I part The phase I part of the study will be initiated with 6 -12 patients enrolled within 1- 8 weeks after surgery to receive GM -CSF given 10- 15 minutes before TG01. Gemcitabine will be started at least 3 weeks after the initiation of immunotherapy but not later than 12 weeks after surgery. Note that, in some centres where transaminases are > 2.5 x Upper Limit of Normal Limit (UNL) at the time of chemotherapy, 5- FU/Leucovorin may be substituted. However, the number of patients in the study refers to those receiving gemcitabine and therefore, for every patient who receives 5- FU only rather than gemcitabine, a further patient will be added. Initially 6 patients will be treated with GM -CSF/TG01 within 1- 8 weeks after surgery and when these 6 patients have reached W eek 11: • If 0/6 patients have an immune response and/or there are >3/6 patients with GM - CSF/TG01 related dose- limiting toxicities (DLTs) observed, the study will be terminated. • If 1-3/6 patients have an immune response and/or if there are ≤ 3/6 patients with GM-CSF/TG01 related DLTs observed, 6 new patients will be enrolled and will be treated in the same way as the previous pat ients. • If ≥ 4/6 patients have an immune response and ≤ 2/6 patients have a GM- CSF/TG01 related DLT, the phase II study will be initiated. If the enrolment of the phase I part is expanded to 12 patients, then at W eek 11: • If < 4/12 patients have an immune response and/or there are > 4/12 patients with GM-CSF/TG01 related DLT s, the study will be terminated. • If ≥ 4/12 patients have an immune response and ≤ 4/12 patients have a GM- CSF/TG01 related DLT, the p hase II study will be initiated. Phase I I part A further 18-25 patients treated with GM -CSF/TG01 + G emcitabine will be added in the Phase II part of the study to provide a total of up to 3 2 patients in the study as a whole. This Phase II part will comprise 3 groups of patients: • Main group (phase I and phase II) – Patients starting vaccination and receiving chemotherapy later . Treatment schedule is described in Figure 3: “ Treatment Syne qua non study no: TAX12001 Targovax ASA study no: CT TG01 -01 Date: 02MAY2018 Page 7 of 21 Version: Amendment 1.0 Final 1.0 ST/form/010/10 schedule for patients starting vaccination and receiving chemotherapy later – Main group” of the protocol. • Concomitant group (phase II) – P atients starting vaccination and chemotherapy at the same time, maximum 6 patients. Treatment schedule is described in Figure 4: “Treatment schedule for patients starting vaccination and chemotherapy at the same time – concomitant group” of the protocol. • Modified vaccination group (phase II) – P atients starting vaccination according to a modified schedule of administration of GM -CSF/TG01 and receiving chemotherapy later, up to 13 patients. Treatment sc hedule is described in Figure 5: “Treatment schedule for patients starting vaccination and receiving chemotherapy later – Modified vaccination group” of the protocol. Patients who are withdrawn for reasons other than toxicity may be replaced if they receiv ed less than 4 weeks of vaccination and have not started gemcitabine. 3.3 Visit Structure Patient s will be assessed according to the visit schedule s described in Table 1: Schedule of Visits , Table 2: Schedule of Visits – Concomitant group, and Table 3: Schedul e of Visits – Modified vaccination group of the protocol. 3.4 Sample Size No formal sample size has been calculat ed. Six to 12 patients in the Phase 1 part of the study and up to 32 patient s in total in the study are deemed sufficient to assess the safety and immune response in this pilot study and will give an early indication of efficacy in terms of disease- free survival ( DFS) and overall survival ( OS) when compared to historical controls (Oettle 2007 and Neoptelemos 2010) . 3.5 Changes from the Protocol Planned Analysis Section 6.