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

Launched by SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT JOHNS HOPKINS · Aug 18, 2021

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment called a mutant KRAS-targeted long peptide vaccine, designed for patients who are at high risk of developing pancreatic cancer. The study aims to see if this vaccine is safe and if it can help the body’s immune system respond better to potential cancer development. Participants will be closely monitored to evaluate the vaccine’s effects, and the trial is currently recruiting individuals who meet specific criteria.

To be eligible for this trial, participants must be at high risk for pancreatic cancer due to factors such as a family history of the disease or genetic mutations that increase their likelihood of developing it. For example, individuals aged 55 or older with a family history of pancreatic cancer, or those with certain genetic mutations, may qualify. Participants will undergo regular monitoring and may receive the vaccine alongside other routine care. It's important to note that there are specific health guidelines that participants must meet to join, and they will need to provide informed consent before starting the study. This trial is a significant step towards better understanding and potentially preventing pancreatic cancer in high-risk individuals.

Gender

ALL

Eligibility criteria

• 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.