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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Recruiting

CT.gov ID

NCT05013216

Collaborator

Stand Up To Cancer (Other)

Enrollment

Location

Arm

48.7

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
High Risk Cancer Pancreatic Cancer	Drug: KRAS peptide vaccine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Apr 11, 2022

Anticipated Primary Completion Date :

May 1, 2026

Anticipated Study Completion Date :

May 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KRAS peptide vaccine	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 Other Names: Hiltonol® (Poly-ICLC)

Arm

Intervention/Treatment

Experimental: KRAS peptide vaccine

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

Other Names:

Hiltonol® (Poly-ICLC)

Outcome Measures

Primary Outcome Measures

Number of participants experiencing study drug-related toxicities [2 years]
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
Maximal percentage of change of interferon (IFN-γ) producing mutant-KRAS-specific CD8 and CD4 T cells [Baseline and 2 years]
Maximal percent change after vaccination compared to pre-vaccination baseline compared to end of study treatment.

Secondary Outcome Measures

Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5, 13 and 17 weeks. [5, 13, and 17 weeks]
Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5, 13 and 17 (EOT) weeks after vaccination compare to pre-vaccination baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

/= 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.