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

J1994

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.

2020-05-28

2025-08-08

2025-08-08

Recruiting

Early phase I

30

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.

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2024-03-01