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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05013216
• Other study ID #: J2177
• Secondary ID: IRB00288752
• Status: Recruiting
• Phase: Phase 1
• Start date: April 11, 2022
• Est. completion date: May 1, 2026

Study information

• Verified date: September 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Colleen Apostal, RN
• Phone: 410-614-3644
• Email: GIClinicalTrials[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 1 study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine with poly-ICLC adjuvant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: May 1, 2026
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

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.
• 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.
• 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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• KRAS peptide vaccine
KRAS peptide vaccine will be administered on Prime week 1, 3, and 5. Boost vaccinations with will be administered at week 13. Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Stand Up To Cancer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants experiencing study drug-related toxicities	Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0	1.5 years
Primary	Maximal percentage of change of interferon (IFN-?) producing mutant-KRAS-specific CD8 and CD4 T cells	Maximal percent change per patient within 17 weeks after vaccination.	17 weeks
Secondary	Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5 weeks.	Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5 weeks after vaccination compared to pre-vaccination baseline.	Baseline, 5 weeks
Secondary	Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 13 weeks.	Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 13 weeks after vaccination compared to pre-vaccination baseline.	Baseline 13 weeks
Secondary	Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 17 weeks.	Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 17 (EOT) weeks after vaccination compared to pre-vaccination baseline.	Baseline,17 weeks