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

• Status: Recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Phase 1 study for patients with resected PDAC after neoadjuvant and/ or adjuvant chemotherapy and/or radiation, as well as patients with metastatic MSS CRC who have progressed on 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Bristol-Myers Squibb
• Treatments: Ipilimumab; Nivolumab; Poly ICLC; Vaccines

Criteria

Inclusion Criteria:

• Age ≥18 years.

• 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 progression on 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.

• 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) 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.

• 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.

• For metastatic MSS CRC cohort, any peritoneal involvement by the tumor.

• For metastatic MSS CRC cohort, any radiological or clinical pleural effusions or ascites.

• For metastatic MSS CRC cohort, patients on parenteral nutrition.

• For metastatic CRC cohort, patients with any single liver metastases greater than 5 cm or greater > 50% liver involvement.

• For metastatic MSS CRC cohort, history of malignant bowel obstruction.