Status:
ACTIVE_NOT_RECRUITING
Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected Mismatch Repair Protein (MMR-p) Colorectal and Pancreatic Cancer
Lead Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborating Sponsors:
Bristol-Myers Squibb
National Cancer Institute (NCI)
Conditions:
Colorectal Cancer
Pancreatic Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
Phase 1 study for patients with resected PDAC after neoadjuvant and/ or adjuvant chemotherapy and/or radiation, as well as patients with metastatic colorectal cancer who have exposure to 2 or more lin...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- PDAC or metastatic MSS CRC Cohort:
- Have histologically or cytologically - proven cancer of the pancreas (PDA) or MSS colorectal (CRC) in one of the following categories:
- PDAC must have no evidence of disease and last dose of neoadjuvant and/or adjuvant chemotherapy/radiation therapy/or surgery must be \< 6 months from study entry.
- Metastatic MSS CRC after exposure to 2 more lines of chemotherapy in the metastatic setting including 5-flurouracil, irinotecan, and oxaliplatin exposure. Patients treated with FOLFOXIRI may enroll after progression or intolerance to that regimen.
- For metastatic MSS CRC cohort, must have tumor lesions amenable to repeated biopsy, and patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the Principal Investigator).
- For metastatic MSS CRC patients, must have measurable disease per RECIST 1.1.
- Reinduction Treatment Cohort:
- Have a single site of locoregional recurrence or distant metastasis noted on imaging \> 12 months after the first dose of the mutant KRAS peptide vaccine with poly-ICLC adjuvant.
- Have completed definitive treatment for solitary recurrence per standard-of-care (e.g. surgical resection, radiation, and/or chemotherapy) \<6 months prior to screening for reinduction treatment.
- Both Cohorts:
- \*Age ≥18 years.
- Have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping.
- Have one of the KRAS mutations included in the vaccine at the time of vaccination 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.
- 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.
- Systemic or topical steroids corticosteroids at immunosuppressive doses (\> 10 mg/day of prednisone or equivalent). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- 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.
- PDAC or metastatic MSS CRC Cohort: 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.
- For metastatic MSS CRC and Reinduction Treatment Cohorts, any peritoneal involvement by the tumor.
- For metastatic MSS CRC and Reinduction Treatment Cohorts, any radiological or clinical pleural effusions or ascites.
- For metastatic MSS CRC and Reinduction Treatment Cohorts, patients on parenteral nutrition.
- For metastatic MSS CRC and Reinduction Treatment Cohorts, patients with any single liver metastases greater than 5 cm or greater \> 50% liver involvement.
- For metastatic MSS CRC and Reinduction Treatment Cohorts, history of malignant bowel obstruction.
Exclusion
Key Trial Info
Start Date :
May 28 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 1 2027
Estimated Enrollment :
27 Patients enrolled
Trial Details
Trial ID
NCT04117087
Start Date
May 28 2020
End Date
June 1 2027
Last Update
December 3 2025
Active Locations (1)
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1
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231