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

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

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

Conditions
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High Risk Cancer, Pancreatic Cancer

Intervention / Treatment
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* Drug: KRAS peptide vaccine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KRAS peptide vaccine<br> | Drug: KRAS peptide vaccine<br>* 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<br>* Other names: Hiltonol® (Poly-ICLC);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Maximal percentage of change of interferon (IFN-γ) producing mutant-KRAS-specific CD8 and CD4 T cells | Maximal percent change per patient within 17 weeks after vaccination. | 17 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KRAS Peptide Vaccine, Neoantigen Vaccines, Cancer Vaccines, Immunotherapy, Pancreatic Ductal Adenocarcinoma (PDAC)