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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; High Risk Cancer
• Intervention / Treatment: Drug: KRAS peptide vaccine

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joann Santmyer, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
• Study Contact Backup: Name: Colleen Apostal, 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: Neeha Zaidi, MD
      • Contact: Trish Brothers, RN; Phone Number: 410-614-3644; Email: GIClinicaltrials@jhmi.edu
      • Contact: Joann Santmyer, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

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
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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Stand Up To Cancer
• Investigators: Principal Investigator: Neeha Zaidi, 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): May 1, 2026
• Study Completion (Estimated): May 1, 2026

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 (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cancer Vaccines; Immunotherapy; Pancreatic Ductal Adenocarcinoma (PDAC); Neoantigen Vaccines; KRAS Peptide Vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Interferon Inducers; 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