Clinical Trials /

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

NCT04117087

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: J1994
  • SECONDARY ID: IRB00210915
  • NCT ID: NCT04117087

Conditions

  • Colorectal Cancer
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
KRAS peptide vaccineHiltonol® (Poly-ICLC)KRAS peptide vaccine, Nivolumab, and Ipilimumab
NivolumabOPDIVOKRAS peptide vaccine, Nivolumab, and Ipilimumab
IpilimumabYERVOY®KRAS peptide vaccine, Nivolumab, and Ipilimumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
KRAS peptide vaccine, Nivolumab, and IpilimumabExperimental
  • KRAS peptide vaccine
  • Nivolumab
  • Ipilimumab

Eligibility 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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants experiencing study drug-related toxicities
Time Frame:4 years
Safety Issue:
Description:Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

Secondary Outcome Measures

Measure:Number of months from the date of first treatment until first documented disease recurrence or death
Time Frame:4 years
Safety Issue:
Description: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).
Measure:Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells
Time Frame:Baseline, 4 years
Safety Issue:
Description:Percent change pre-vaccination baseline compared to end of study.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • 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

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