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

Trial ID: NCT04117087

Interventional - Phase 1 - Active, not recruiting

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 lines of chemotherapy, 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.

Conditions

• Colorectal Cancer
• Pancreatic Cancer

Interventions

• KRAS peptide vaccine
• Nivolumab
• Ipilimumab

Eligibility

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.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bristol-Myers Squibb, National Cancer Institute (NCI), National Institutes of Health (NIH)

Source: ClinicalTrials.gov

Search more clinical trials on myTomorrows