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

Launched by SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT JOHNS HOPKINS · Oct 3, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with certain types of colorectal and pancreatic cancer. The researchers want to see how safe and effective a combination of a specialized vaccine (designed to target specific cancer cells) and two immunotherapy drugs (nivolumab and ipilimumab) is for patients who have already had surgery and treatment for their cancer. The goal is to help the body’s immune system recognize and fight the cancer more effectively.

To be eligible for this trial, participants must be at least 18 years old and have either pancreatic cancer that has been surgically removed or metastatic colorectal cancer that has not responded to other treatments. They also need to provide a sample of their tumor tissue for testing. Participants can expect to undergo regular monitoring and have the opportunity to receive a potentially promising treatment. It’s important to know that certain health conditions and previous treatments might prevent someone from joining the study, so discussing eligibility with a healthcare provider is crucial.

Gender

ALL

Eligibility criteria

• 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.