Neoantigen Peptide Vaccine Strategy In Pancreatic Cancer Patients Following Surgical Resection And Adjuvant Chemotherapy

Study Overview

Neoantigen Peptide Vaccine Strategy in Pancreatic Cancer Patients Following Surgical Resection and Adjuvant Chemotherapy

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.

N/A

Pancreas Cancer
Pancreatic Cancer
Cancer of the Pancreas

BIOLOGICAL: Neoantigen Peptide Vaccine
DRUG: Poly ICLC
PROCEDURE: Blood for immune monitoring

201908124
P50CA196510-03 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-05-15	Results First Submitted 2023-05-01	Last Update Submitted that met QC Criteria 2024-06-20
First Submitted that Met QC Criteria 2019-05-15	Results First Submitted that Met QC Criteria 2023-05-26	Last Update Posted (ACTUAL) 2024-07-17
First Posted (ACTUAL) 2019-05-20	Results First Posted 2023-05-31	Last Verified 2024-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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 b	BIOLOGICAL: Neoantigen Peptide Vaccine • Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection. DRUG: Poly ICLC • Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection. PROCEDURE: Blood for immune monitoring -Baseline, day 1, day 22, day 50, day 78, week 25, and week 73

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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 b

BIOLOGICAL: Neoantigen Peptide Vaccine

• Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.

DRUG: Poly ICLC

• Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection.

PROCEDURE: Blood for immune monitoring

-Baseline, day 1, day 22, day 50, day 78, week 25, and week 73

Primary Outcome Measures	Measure Description	Time Frame
Safety of Neoantigen Peptide Vaccine as Measured by the Number of Serious Adverse Events	-Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.	Through 30 days following completion of treatment (median follow-up of 107 days, full range of 88-157 days)

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants With Immune Response as Measured by ELISPOT Analysis	The ELISpot assay was performed after in vitro culture of patient PBMC with neoantigen peptide for ~12 days. The number of spot-forming T cells, a surrogate for the number of neoantigen-specific T cells, was determined after neoantigen peptide re-stimulation for the duration of the assay (48 hours) and compared to that of control cells that were not re-stimulated with neoantigen during the assay. Independent t tests between pre- and post-vaccination PBMCs were performed.	Baseline through week 52
Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD4)	Multiparametric flow cytometry was performed as a second readout to characterize the neoantigen-specific T cell response. Markers included CD4, CD8, IFNγ, and a viability marker. After culture, as described above, T cells were stimulated overnight with/without neoantigen and stained with fluorescent antibodies specific for the various markers. Data were analyzed by comparing, between pre- and post-vaccination PBMCs, the percent ratio of IFNγ+ CD4/CD8 cells with neoantigen stimulation over those without stimulation; a >2-fold increase in response after vaccination was considered positive.	Baseline through week 52
Number of Participants With Immune Response as Measured by Multiparametric Flow Cytometry (CD8)	Multiparametric flow cytometry was performed as a second readout to characterize the neoantigen-specific T cell response. Markers included CD4, CD8, IFNγ, and a viability marker. After culture, as described above, T cells were stimulated overnight with/without neoantigen and stained with fluorescent antibodies specific for the various markers. Data were analyzed by comparing, between pre- and post-vaccination PBMCs, the percent ratio of IFNγ+ CD4/CD8 cells with neoantigen stimulation over those without stimulation; a >2-fold increase in response after vaccination was considered positive.	Baseline through week 52

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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
total bilirubin≤1.5 X institutional upper limit of normal (subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated bilirubin is <1.5 x ULN)
AST≤ X institutional upper limit of normal
creatinine≤1.5 X institutional upper limit of normal
International Normalized Ratio (INR) and activated partial thromboplastin time (PTT) < 1.5 x ULN provided the patient is not on anticoagulation therapy.

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Able to understand and willing to sign an IRB approved written informed consent document.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Institutes of Health (NIH)
National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: William E Gillanders, M.D., Washington University School of Medicine

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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