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Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT04117087
Recruitment Status : Not yet recruiting
First Posted : October 7, 2019
Last Update Posted : October 7, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
Phase 1 study for patients with resected PDAC and mismatch repair (MMR)-p colorectal cancer (CRC) to evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with poly-ICLC adjuvant in combination with nivolumab and ipilimumab after adjuvant standard of care treatment.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Pancreatic Cancer Drug: KRAS peptide vaccine Drug: Nivolumab Drug: Ipilimumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected MMR-p Colorectal and Pancreatic Cancer
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: KRAS peptide vaccine, Nivolumab, and Ipilimumab Drug: KRAS peptide vaccine
  1. KRAS peptide vaccine will be administered on days 1, 8, 15 and 22. Five boost vaccinations with will be administered at 8-9 week intervals (on weeks 13, 22, 31, 40, and 49).
  2. Drug: 1.8 mg KRAS peptide vaccine + 0.3mg Poly-ICLC
Other Name: Hiltonol® (Poly-ICLC)

Drug: Nivolumab
  1. Nivolumab 360 mg will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of each 21 day cycle.
  2. Drug: 360 mg IV
Other Name: OPDIVO

Drug: Ipilimumab
  1. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of Cycles 1, 3, 5, 7, 9, 11, 13, 15 and 17 of the study or every 6 weeks for a total of a year.
  2. Drug: 1mg/kg IV
Other Name: YERVOY®




Primary Outcome Measures :
  1. Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]
    Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

  2. Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 16 weeks [ Time Frame: Baseline, 16 weeks ]
    Evaluated by the fold change in interferon-producing mutant-KRAS-specific cluster of differentiation 8 (CD8) and cluster of differentiation 4 (CD4) T cells after vaccination at 16 weeks compare to pre-vaccination baseline.


Secondary Outcome Measures :
  1. Number of months from the date of first treatment until first documented disease recurrence or death [ Time Frame: 4 years ]
    Number of months from the date of first treatment until first documented disease recurrence or death. This will be used to assess Disease-free Survival (DFS).

  2. Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells [ Time Frame: Baseline, 4 years ]
    Percent change pre-vaccination baseline compared to end of study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years.
  • Have histologically or cytologically - proven cancer of the pancreas or microsatellite stable (MSS)-colon.
  • Does not have measurable disease by imaging.
  • Have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping.
  • Have one of the six KRAS mutations (KRASG12C, KRASG12V, KRASG12D, KRASG12A, KRASG13D or KRASG12R) in vaccine expressed in tumor.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Life expectancy of greater than 6 months.
  • Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
  • 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.
  • Ability to understand and willingness to sign a written informed consent document.
  • Last dose of adjuvant chemotherapy or radiation therapy administered within 6 months of screening tests.

Exclusion Criteria

  • If expected to require any other form of systemic or localized antineoplastic therapy while on study.
  • Within 2 weeks prior to first dose of study drug.

    • Any systemic or topical corticosteroids at immunosuppressive agents.
    • Any palliative or adjuvant radiation or gamma knife radiosurgery.
    • Any chemotherapy.
  • Within 4 weeks prior to first dose of study drug.

    • Any investigational cytotoxic drug.
    • Any investigational device.
    • Has received a live vaccine.
    • Received any allergen hyposensitization therapy.
    • Received any growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin.
    • Any major surgery.
  • Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), etc.).
  • Hypersensitivity reaction to any monoclonal antibody.
  • Known history or evidence of brain metastases.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
  • Known history or concurrent interstitial lung disease.
  • Has a pulse oximetry < 92% on room air.
  • Requires the use of home oxygen.
  • 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.
  • Has been diagnosed with another cancer or myeloproliferative disorder within the past 5 year.
  • Has a diagnosis of immunodeficiency.
  • Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04117087


Contacts
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Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu
Contact: Ellen Lilly-Forman, RN 443-287-4961 lillyel@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Bristol-Myers Squibb
Investigators
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Principal Investigator: Nilofer Azad, MD Johns Hopkins Medical Institution

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT04117087     History of Changes
Other Study ID Numbers: J1994
IRB00210915 ( Other Identifier: Johns Hopkins Medical Institution )
First Posted: October 7, 2019    Key Record Dates
Last Update Posted: October 7, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
KRAS Peptide Vaccine
Nivolumab
Ipilimumab
Anti-PD-1
Anti-CTLA-4
Neoantigen Vaccines
Cancer Vaccines
Immunotherapy
Colon Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
Resected MMR-p Colorectal Cancer
Resected MMR-p Pancreatic Cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Pancreatic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Nivolumab
Ipilimumab
Vaccines
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents
Interferon Inducers