膵臓がん発症のリスクが高い患者向けの変異型KRAS - 標的化長鎖ペプチドワクチン

Inclusion Criteria:

Cohort A: Must 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 associated with an estimated lifetime risk of pancreatic cancer of ~10% or higher):

  • >/=40 years old and the Patient is a carrier of 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 CLIA-certified laboratory.

  o High Risk Group 3 (Germline mutation carriers with an associated 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 non-polyposis 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 IPMN or parenchymal abnormalities consistent with PanIN.

  • Cohort B: Patients must have clinical, radiographic, or histologic evidence of pancreatic cystic neoplasm with high-risk features 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.

• Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.

• Ability to understand and willingness to sign a written informed consent document.

• Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.

• Men must use acceptable form of birth control while on study.

Exclusion Criteria:

• If expected to require any other form of systemic or localized antineoplastic therapy while on study.

• Within 4 weeks prior to first dose of study drug.

  o Any systemic or topical corticosteroids at immunosuppressive agents.

• Within 4 weeks prior to first dose of study drug.

  • Any investigational device.
  • Has received a live vaccine.
  • Received any allergen hyposensitization therapy.
  • Any major surgery.

• Infection with HIV or hepatitis B or C.

• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements monoclonal antibody.

• Has a diagnosis of immunodeficiency.

• Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.

• Unwilling or unable to follow the study schedule for any reason.

• Are pregnant or breastfeeding.