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

This Phase 1 study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine with poly-ICLC adjuvant for patients who have been identified to be at risk of developing pancreatic cancer.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; High Risk Cancer
• Intervention / Treatment: Drug: Cohort A: Patients at high risk of developing pancreatic cancer.; Drug: Cohort B: Patients must have evidence of a pancreatic cystic neoplasm

Detailed Description

This study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with poly-ICLC adjuvant. The primary endpoints of this study are to determine the safety of administering the KRAS peptide vaccine with poly-ICLC adjuvant and to assess the maximal percent change of IFN-γ-producing mutant-KRAS-specific T cells per patient at any time after vaccination. Twenty five patients will be enrolled to achieve 20 evaluable patients for Cohort A. Twelve patients will be enrolled to achieve 10 evaluable patients for Cohort B.

For all patients, the study will consist of a screening phase, treatment phase, and a follow-up visit. All subjects will have the option remaining on study with annual follow-up visits that begin approximately one year after the last vaccine dose and continue annually thereafter until study closure.

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer Center
      • Principal Investigator: Nilofer Azad, MD
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Patients at high risk of developing pancreatic cancer.; Patients will include those who have undergone pancreatic imaging with MRI or CT or EUS and found to have one or more pancreatic imaging abnormalities such as a pancreatic cyst consistent with an intraductal papillary mucinous neoplasm (IPMN) or parenchymal changes consistent with pancreatic intraepithelial neoplasia (PanIN). additionally patients with: familial pancreatic cancer relatives; germline mutation carriers with an estimated lifetime risk of pancreatic cancer of ~10% or higher; germline mutation carriers with an estimated lifetime risk of pancreatic cancer of ~5%, all detailed in Section 3.1.1. These patients must also (as defined in Section 3.1.2).	Drug: Cohort A: Patients at high risk of developing pancreatic cancer.; KRAS peptide vaccine with poly-ICLC adjuvant will be administered on Prime week 1, 3, and 5. Boost vaccinations with will be administered at week 13. All subjects will return to the study site approximately 28 days (+ 7 days) after the last vaccination for an End of Treatment (EOT) and safety evaluation.; Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC; Other Names: Hiltonol® (Poly-ICLC)
Experimental: Cohort B: Patients must have evidence of a pancreatic cystic neoplasm; Patients must have clinical, radiographic, or histologic evidence of a pancreatic cystic neoplasm with high-risk features warranting surgical resection per the discretion of the treating hepatobiliary surgeon. In addition, cyst fluid analysis must demonstrate the presence of one of the six KRAS mutations included in the study vaccine. Germline mutation testing or a positive family history of pancreatic cancer is not required for enrollment in Cohort B.	Drug: Cohort B: Patients must have evidence of a pancreatic cystic neoplasm; Patients will receive KRAS peptide vaccine with poly-ICLC adjuvant as two prime vaccinations on weeks 1 and 2. Surgery is considered standard of care. Surgery will occur at the discretion of the treating hepatobiliary surgeon and is not dictated by this protocol. Subjects will return to the study site approximately at week 4 (+ 7 days) for a safety evaluation prior to surgery. Subjects will have an End of Treatment (EOT) visit at study Week 8 (+ 7 days).; Other Names: Hiltonol® (Poly-ICLC)

What is the study measuring?

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 (Cohort A)
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 (Cohort A)
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 (Cohort A)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 1 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, 1 week (Cohort B)
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 4 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, 4 weeks (Cohort B)
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 8 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, 8 weeks (Cohort B)

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI); Stand Up To Cancer
• Investigators: Principal Investigator: Nilofer Azad, MD, Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): May 1, 2031

Study Registration Dates

• First Submitted: August 18, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Cancer Vaccines; Immunotherapy; Pancreatic Ductal Adenocarcinoma (PDAC); Neoantigen Vaccines; KRAS Peptide Vaccine
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Anti-Infective Agents; Immunologic Factors; Physiological Effects of Drugs; Gastrointestinal Agents; Antiviral Agents; Interferon Inducers; Laxatives; poly ICLC
• Other Study ID Numbers: J2177; IRB00288752 (Other Identifier: Johns Hopkins Medical Institution)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No