Vaccine targeting mutant KRAS for patients at high risk of pancreatic cancer

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

This study is testing a new vaccine for people at high risk of pancreatic cancer to see if it can safely boost their immune response against a specific cancer-related mutation.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT05013216 on ClinicalTrials.gov

What this trial studies

This Phase 1 study evaluates the safety and immune response to a pooled mutant-KRAS peptide vaccine combined with a poly-ICLC adjuvant in patients identified as high risk for developing pancreatic cancer. The study aims to determine the safety of the vaccine and measure the immune response by assessing the change in specific T cells after vaccination. It will enroll a total of 37 patients across two cohorts, with follow-up visits planned annually after treatment. The study includes a screening phase, treatment phase, and follow-up to monitor patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include individuals at high risk for pancreatic cancer due to familial history or specific genetic mutations.

Not a fit: Patients without a significant family history of pancreatic cancer or those not classified as high risk will likely not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccine could provide a preventive strategy for patients at high risk of developing pancreatic cancer.

How similar studies have performed: Other studies targeting KRAS mutations have shown promise, indicating potential for success with this approach.

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.

Where this trial is running

Baltimore, Maryland

• Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Nilofer Azad, MD — Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Medical Institution
• Study coordinator: Colleen Apostol, RN

Conditions High Risk Cancer; Pancreatic Cancer; KRAS Peptide Vaccine; Neoantigen Vaccines; Cancer Vaccines; Immunotherapy; Pancreatic Ductal Adenocarcinoma