A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Neoantigen Peptide Vaccine Strategy in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy
Overview
- Phase
- Phase 1
- Intervention
- Neoantigen Peptide Vaccine
- Conditions
- Pancreas Cancer
- Sponsor
- Washington University School of Medicine
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Safety of Neoantigen Peptide Vaccine as Measured by the Number of Serious Adverse Events
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen peptide vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen peptide vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be co-administered with poly-ICLC. The hypothesis of this study is that neoantigen peptide vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma; mixed histology will be included as long as the predominant histology is adenocarcinoma.
- •Completed an R0 or R1 surgical resection as determined by pathology
- •Pathology review demonstrates tumor cellularity no less than 30% in quantities sufficient to obtain 6-8 1mm biopsies from the original FFPE blocks.
- •At least 18 years of age.
- •Life expectancy of \> 12 months.
- •ECOG performance status ≤ 2
- •Normal bone marrow and organ function as defined below:
- •WBC\>=3,000/μL
- •absolute neutrophil count\>=1,500/μL
- •platelets\>=100,000/μL
Exclusion Criteria
- •Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma.
- •Received neoadjuvant chemotherapy for their pancreatic adenocarcinoma
- •Evidence of disease recurrence or metastasis following surgical resection at any time prior to the first vaccination administration. Most patients will undergo restaging midway through adjuvant chemotherapy and at the completion of therapy; however, timing of imaging is at the discretion of the patient's medical oncologist.
- •History of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or LCIS/DCIS of the breast
- •Known allergy, or history of serious adverse reaction to vaccines or TLR agonists such as anaphylaxis, hives, or respiratory difficulty.
- •Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, and/or other functional abnormality that would jeopardize the health and safety of the participant as determined by the investigator based on medical history, physical examination, laboratory values, and/or diagnostic studies.
- •A psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record
- •Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for \> 7 consecutive days. Any patients receiving steroids should be discussed with the PI to determine if eligible.
- •Pregnant and/or breastfeeding.
- •Known HIV-positive status. These patients are ineligible because of the potential inability to generate an immune response to vaccines.
Arms & Interventions
Neoantigen Peptide Vaccine
The schedule for vaccination will be Days 1, 4, 8, 15, and 22 (delays of up to 96 hours are allowed for each dose based on the adverse events experienced). Additional vaccinations will be given on Days 50 and 78 (+/- 2 weeks). The first vaccine dose may be administered following confirmation of disease-free status and within 90 days following date of repeat imaging. All study injections will be given subcutaneously and co-administered with poly-ICLC by a trained healthcare provider.
Intervention: Neoantigen Peptide Vaccine
Neoantigen Peptide Vaccine
The schedule for vaccination will be Days 1, 4, 8, 15, and 22 (delays of up to 96 hours are allowed for each dose based on the adverse events experienced). Additional vaccinations will be given on Days 50 and 78 (+/- 2 weeks). The first vaccine dose may be administered following confirmation of disease-free status and within 90 days following date of repeat imaging. All study injections will be given subcutaneously and co-administered with poly-ICLC by a trained healthcare provider.
Intervention: Poly ICLC
Neoantigen Peptide Vaccine
The schedule for vaccination will be Days 1, 4, 8, 15, and 22 (delays of up to 96 hours are allowed for each dose based on the adverse events experienced). Additional vaccinations will be given on Days 50 and 78 (+/- 2 weeks). The first vaccine dose may be administered following confirmation of disease-free status and within 90 days following date of repeat imaging. All study injections will be given subcutaneously and co-administered with poly-ICLC by a trained healthcare provider.
Intervention: Blood for immune monitoring
Outcomes
Primary Outcomes
Safety of Neoantigen Peptide Vaccine as Measured by the Number of Serious Adverse Events
Time Frame: Through 30 days following completion of treatment (median follow-up of 107 days, full range of 88-157 days)
-Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.
Secondary Outcomes
- Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD8)(Baseline through week 52)
- Number of Participants With Immune Response as Measured by ELISPOT Analysis(Baseline through week 52)
- Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD4)(Baseline through week 52)