A Phase 2 Double-Blind, Placebo Controlled, Multi-center Adjuvant Trial of the Efficacy, Immunogenicity, and Safety of GI-4000; an Inactivated Recombinant Saccharomyces cerevisiae Expressing Mutant Ras Protein Combined with a Gemcitabine Regimen Versus a Gemcitabine Regimen with Placebo, in Patients with Post-resection R0/R1 Pancreatic Cancer with Tumor Sequence Confirmation of Ras Mutations.

INTERVENTION: Product Name: GI‐4000 series of products Product Code: GI‐4014, GI‐4015, GI‐4016, GI‐4020 Pharmaceutical Form: Suspension for injection INN or Proposed INN: GI‐4014, GI‐4015, GI‐4016, GI‐4020 CAS Number: NA Current Sponsor code: GI‐4000 Other descriptive name: NA Concentration unit: million organisms/ml million organisms/millilitre Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Trade Name: Gemzar Product Name: gemcitabine Product Code: NA Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Gemcitabine hydrochloride CAS Number: 95058‐81‐4 Current Sponsor code: Standart of Care Other descriptive name: NA Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 1000‐ CONDITION: Pancreatic Cancer, post resection R0/R1 status, with tumor sequence confirmation of Ras mutations ; MedDRA version: 17.0 Level: LLT Classification code 10033575 Term: Pancreas cancer System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of weekly followed by monthly doses of GI‐4000 in combination with adjuvant gemcitabine versus adjuvant gemcitabine with placebo in post‐resection pancreatic cancer patients, as measured by time to recurrence. Primary end point(s): Recurrence free survival at 15 months after randomization. Secondary Objective: 1. To evaluate secondary endpoints of disease response as measured by the duration of recurrence‐free survival, time to mortality, duration of overall survival, changes in symptom scores, and CA 19‐9 levels.; 2.To evaluate the immunogenicity of GI‐4000, as measured by antigen specific T‐cell responses. Genome wide association studies including full length genomic sequencing in a subset of subjects will also be applied to the current study to evaluate whether genetic determinants can influence immune response to blinded study therapy (GI‐4000 versus placebo) as well as clinical outcomes such as time to disease recurrence and mortality.; 3. To evaluate the safety of GI‐4000 in a regimen combined with gemcitabine, as measured by SAEs, discontinuation due to AEs, and dosing interruptions/reductions due to AEs.; ; Timepoint(s) of evaluation of this end point: Duration of recurence free survival is number of days from randomization to the earlier date of disease progression or death due to any cause. INCLUSION CRITERIA: 1 Subjects must have resectable pancreas cancer, ductal adenocarcinoma type, with post‐resection confirmation of non‐metastatic disease. 2 Confirmed product related mutation in Ras from tumor sample. 3 ECOG performance status (PS) of =2 prior to randomization. 4 Confirmed R0 or R1 status post‐resection. 5 Negative scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae. 6 Age =18 years. 7 Signed, written, informed consent from the patient or legal representative before any study‐specific procedures are performed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50 SECONDARY OUTCOME: Secondary end point(s): 1. Time to mortality ; 2. Biochemical recurrence (CA19‐9) ; 3. Duration of recurrence‐free survival measured from the date of randomization; 4. Duration of recurrence‐free survival measured from the date of surgery; 5. Duration of overall survival measured from the date of randomization; 6. Duration of overall survival measured from the date of surgery; 7. Longitudinal changes in CA 19‐9 levels relative to the baseline level; 8. Longitudinal changes in EORTC QLQ C30 symptom scores from baseline for nausea/vomiting, pain, and fatigue; 9. Longitudinal changes in ECOG performance status scores from baseline; Timepoint(s) of evaluation of this end point: 1. Time to mortality ‐ from randomization to subject's death; 2. Biochemical recurrence (CA19‐9), Longitudinal changes in CA 19‐9 levels relative to the baseline level, Longitudinal changes in EORTC QLQ C30 symptom scores, Longitudinal changes in ECOG performance status scores ‐ from screening to disease progression; 3. Duration of recurrence‐free survival measured from the date of randomization, Duration of overall survival measured from the date of randomization ‐ from randomization to disease progression or death; 4. Duration of recurrence‐free survival measured from the date of surgery, Duration of overall survival measured from the date of surgery ‐ from the surgery to disease progression or death; ;