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

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

Tracking Information

• First Submitted Date: October 3, 2019
• First Posted Date: October 7, 2019
• Last Update Posted Date: October 7, 2019
• Estimated Study Start Date: January 2020
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2019)

• 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
• 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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 3, 2019)

• 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).
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colorectal Cancer
• Pancreatic Cancer

Intervention

• 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®

Study Arms

Experimental: KRAS peptide vaccine, Nivolumab, and Ipilimumab

Interventions:

• Drug: KRAS peptide vaccine
• Drug: Nivolumab
• Drug: Ipilimumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: October 3, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Susan Sartorius-Mergenthaler, RN; 410-614-3644; Sartosu@jhmi.edu

Contact: Ellen Lilly-Forman, RN; 443-287-4961; lillyel@jhmi.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04117087
• Other Study ID Numbers: J1994; IRB00210915 ( Other Identifier: Johns Hopkins Medical Institution )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Nilofer Azad, MD; Johns Hopkins Medical Institution

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: October 2019