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

NCT05013216 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J2177IRB00288752
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Cancer; High Risk Cancer

Keywords

KRAS Peptide Vaccine; Neoantigen Vaccines; Cancer Vaccines; Immunotherapy; Pancreatic Ductal Adenocarcinoma (PDAC)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5 weeks.

  Baseline, 5 weeks (Cohort A)

• Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 13 weeks.

  Baseline, 13 weeks (Cohort A)

• Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 17 weeks.

  Baseline,17 weeks (Cohort A)

Other Outcomes (3)

• Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 1 weeks.

  Baseline, 1 week (Cohort B)

• Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 4 weeks.

  Baseline, 4 weeks (Cohort B)

• Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 8 weeks.

  Baseline, 8 weeks (Cohort B)

Study Arms (2)

Cohort A: Patients at high risk of developing pancreatic cancer.

EXPERIMENTAL

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: 1. familial pancreatic cancer relatives 2. germline mutation carriers with an estimated lifetime risk of pancreatic cancer of \~10% or higher 3. 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.

Cohort B: Patients must have evidence of a pancreatic cystic neoplasm

EXPERIMENTAL

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

Interventions

Cohort A: Patients at high risk of developing pancreatic cancer. DRUG

1. 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. 2. Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC

Also known as: Hiltonol® (Poly-ICLC)

Cohort A: Patients at high risk of developing pancreatic cancer.

Cohort B: Patients must have evidence of a pancreatic cystic neoplasm DRUG

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).

Also known as: Hiltonol® (Poly-ICLC)

Cohort B: Patients must have evidence of a pancreatic cystic neoplasm

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \>/= 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Stand Up To Cancer: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

poly ICLC

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Nilofer Azad, MD

  Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostol, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 19, 2021
• Study Start: April 11, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): May 1, 2031
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)