Mutant KRAS-Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer

Inclusion Criteria

• Cohort A: Must 1) fall into one of the three categories defined as high risk of developing pancreatic cancer and are undergoing pancreatic surveillance AND 2) have documented radiographic evidence of a pancreatic abnormality such as a pancreatic cyst * High risk group 1 (familial pancreatic cancer relatives): ** ≥ 55 years old or 10 years younger than the age of youngest relative with pancreatic cancer, and ** Come from a family with 2 or more members with a history of pancreatic cancer (2 of which have a first-degree relationship consistent with familial pancreatic cancer), and ** Have a first-degree relationship with at least one of the relatives with pancreatic cancer ** If there are 2 or more affected blood relatives, at least 1 must be a first-degree relative of the individual being screened * High risk group 2 (germline mutation carriers with an estimated lifetime risk of pancreatic cancer of ~ 10% or higher): ** ≥ 40 years of age and the patient is a carrier of familial atypical multiple mole melanoma (FAMMM) (p16/CDKN2A) mutation regardless of family pancreas cancer history OR ** ≥ 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and the Patient is a carrier of a known BRCA2, ATM, PALB2 mutation ** Persons with known genetic mutation should have proof of mutation status. Those who had research-related genetic testing must have confirmation by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory * High risk group 3 (germline mutation carriers with an estimated lifetime risk of pancreatic cancer of ~ 5%): ** ≥ 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and ** The patient is a carrier of a known, BRCA1, or HNPCC (hereditary nonpolyposis colorectal cancer or Lynch syndrome, hMLH1, hMSH2, PMS1, hMSH6, EpCAM) gene mutation, and there is ≥ 1 pancreatic cancer in the family, one of whom is a first- or second-degree relative of the subject to be screened ** Persons with known genetic mutation should have proof of mutation status. Those who had research-related genetic testing must have confirmation by a clinical CLIA-certified laboratory
• Cohort A: Patients must have a pancreatic imaging abnormality that is being followed by pancreatic imaging surveillance (EUS and/or MRI and/or CT), such as a pancreatic cyst consistent with an intraductal papillary-mucinous neoplasm (IPMN) or parenchymal abnormalities consistent with pancreatic intraepithelial neoplasia (PanIN)
• Cohort B: Patients must have clinical, radiographic, or histologic evidence of pancreatic cystic neoplasm warranting surgical resection per the discretion of the treating hepatobiliary surgeon
• Cohort B: Patients must have cystic fluid testing that demonstrates the presence of one of the six KRAS mutations included in the study vaccine
• Leukocytes ≥ 3,000/mcL
• Lymphocytes > 500/mm^3
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100 x 10^3/uL
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 1.5 x ULN
• Alkaline phosphatase ≤ 5.0 x ULN
• Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula)
• Ability to understand and willingness to sign a written informed consent document
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]). NOTE: If a patient has a positive or indeterminate serum or urine pregnancy test, then an ultrasound must be done to rule out pregnancy to enroll on trial * WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug plus 4 weeks (duration of ovulatory cycle) for a total of 28 days post-treatment completion * Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 28 days post-treatment completion * At least one barrier method of contraception must be employed by all sexually active patients (male and female), regardless of other methods, to prevent the transfer of body fluids

Exclusion Criteria

• Patient is expected to require any form of systemic or localized antineoplastic therapy while on study
• Any of the following procedures or medications: * Within 4 weeks prior to initiation of study treatment: ** Systemic or topical corticosteroids at immunosuppressive doses (> 10 mg/day of prednisone or equivalent). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Short-term systemic corticosteroids are permitted in the context of treating adverse events (AEs), prophylaxis prior to a diagnostic procedure (e.g., contrast MRI/CT scans) ** Any investigational device ** Non-oncology vaccines containing live virus. Examples include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid vaccine ** Allergen hyposensitization therapy ** Major surgery (excludes other minor procedures such as dental work, skin biopsy, etc)
• Has a known history of human immunodeficiency virus (HIV) (HIV1/2 antibodies), hepatitis B, or hepatitis C infection. (Patients who are hepatitis C antibody positive may be enrolled if they are confirmed with negative viral load at screening)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, cancer, or psychiatric illness/social situations that would limit compliance with study requirements
• Has a diagnosis of immunodeficiency
• Any other sound medical, psychiatric, and/or social reason as determined by the investigator
• Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements
• Patient is unwilling or unable to follow the study schedule for any reason
• Patient is pregnant or breastfeeding