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

Brief summary public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: KRAS peptide vaccine. 1. KRAS peptide vaccine will be administered on cycle 1 (days 1, 8, 15) and R-Cycle 2 Day 1 (R-C2D1). Boost vaccinations with will be administered every 28 days at Reinduction cycle 5, 7, 9, 13. Extended vaccinations will be administered on Reinduction cycles 15 to 18, 19 and beyond (180 days ± 30 days for a total of 5 years on study. 2. Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC

Intervention public domain (ClinicalTrials.gov)

Drug: Nivolumab. 1. Nivolumab will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of each 21 day cycle. Boost Phase will be administered every 28 days on cycles 5 thru 14. 2. Drug: 3mg/kg IV, 480 mg IV

Intervention public domain (ClinicalTrials.gov)

Drug: Ipilimumab. 1. Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10min/+15min) on Day 1 of Cycles 1 and 3 of the study. 2. Drug: 1mg/kg IV

Arm public domain (ClinicalTrials.gov)

Treatment Phase (experimental): KRAS Vaccine Peptide, Nivolumab and Ipilimumab

Arm public domain (ClinicalTrials.gov)

Reinduction Treatment Phase (experimental): KRAS Vaccine Peptide, Nivolumab and Ipilimumab

Primary outcome public domain (ClinicalTrials.gov)

Number of participants experiencing study drug-related toxicities. Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0 Time frame: 2 years.

Primary outcome public domain (ClinicalTrials.gov)

Fold change in interferon-producing mutant-KRAS-specific cytotoxic (CD8) and helper (CD4) T cells at 16 weeks. Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells after vaccination at 16 weeks compare to pre-vaccination baseline. Time frame: Baseline, 16 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Disease Free Survival (DFS). Time frame: 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Percentage change of interferon (IFN)-γ-producing mutant-KRAS-specific CD8 and CD4 T cells. Time frame: 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR) per RECIST 1.1. Time frame: 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival (PFS) for RECIST 1.1. Time frame: 4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS). Time frame: 4 years.

Eligibility public domain (ClinicalTrials.gov)

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 …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 27 participants (actual).