Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery

NCT05111353 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 202205120
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized phase 1 clinical trial to evaluate the safety of an optimized neoantigen synthetic long peptide (SLP) vaccines in pancreatic cancer patients following neoadjuvant chemotherapy. The neoantigen SLP vaccines will incorporate prioritized neoantigens and will be co-administered with poly-ICLC. Patients will be randomized to one of two arms: Arm 1 (neoantigen vaccine following neoadjuvant chemotherapy and surgery) or Arm 2 (neoantigen vaccine following neoadjuvant chemotherapy in the window prior to surgery). Those who are ineligible for vaccine administration including those whose disease progresses or recurs during neoadjuvant chemo or who are otherwise unable to complete surgical resection but who had a personalized neoantigen vaccine manufactured, or significant progress has been made as determined by treating physician, are permitted to receive vaccine injections on study.

Conditions

Pancreas Cancer; Pancreatic Cancer; Cancer of the Pancreas

Outcome Measures

Primary Outcomes (1)

• Safety of neoantigen SLP vaccine as measured by number of subjects experiencing each type of adverse event

  -Adverse events will be characterized according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE).

  Through 4 weeks after completion of last vaccination (estimated to be 108 days)

Secondary Outcomes (2)

• Immunogenicity of neoantigen peptide vaccine as measured by the the number of neoantigen-specific T cells (only Arm 1 and Arm 2)

  Through approximately 2 years and 78 days

• Immunogenicity of neoantigen peptide vaccine as measured by the phenotype of neoantigen-specific T cells (only Arm 1 and Arm 2)

  Through approximately 2 years and 78 days

Study Arms (2)

Arm 1: Vaccine given after neoadjuvant chemotherapy and surgery

EXPERIMENTAL

* The neoantigen peptide vaccine will be manufactured during neoadjuvant chemotherapy. Institutional standard of care chemotherapy will be given. * Peptide and poly-ICLC will be administered intramuscularly on Days 1, 4, 8, 15, 22, 50, and 78 beginning approximately 1 month after surgery. Day 1 should begin approximately 1 month after surgery.

Biological: Optimized neoantigen synthetic long peptide vaccine; Biological: Poly-ICLC

Arm 2: Vaccine given after neoadjuvant chemotherapy but before surgery

EXPERIMENTAL

* The neoantigen peptide vaccine will be manufactured during neoadjuvant chemotherapy. Institutional standard of care chemotherapy will be given. * Peptide and poly-ICLC will be administered intramuscularly on Days 1, 4, 8, 15, and 22 during the chemotherapy holiday, and Days 50 and 78 post-operatively. Optimal timing for Day 1 is 1 week after end of chemotherapy, but Day 1 may be given up to 3 weeks after end of chemotherapy.

Biological: Optimized neoantigen synthetic long peptide vaccine; Biological: Poly-ICLC

Interventions

Optimized neoantigen synthetic long peptide vaccine BIOLOGICAL

Neoantigen vaccines will be provided on a patient-specific basis

Arm 1: Vaccine given after neoadjuvant chemotherapy and surgery; Arm 2: Vaccine given after neoadjuvant chemotherapy but before surgery

Poly-ICLC BIOLOGICAL

Poly-ICLC will be supplied by Oncovir, Inc.

Also known as: Hiltonol

Arm 1: Vaccine given after neoadjuvant chemotherapy and surgery; Arm 2: Vaccine given after neoadjuvant chemotherapy but before surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, newly diagnosed, treatment-naïve patients with localized or borderline resectable adenocarcinoma of the pancreas for whom neoadjuvant chemotherapy is considered appropriate; mixed histology (including adenosquamous). Patients with clinical suspicion of pancreatic adenocarcinoma can be enrolled for pre-treatment biopsy, and must be histologically confirmed to have adenocarcinoma before being treated on study. Patients with squamous carcinoma or neuroendocrine tumor will be excluded.
• Evaluable disease, in the opinion of the treating investigator or PI.
• Tissue specimens available in sufficient quantity to allow for sequencing.
• At least 18 years of age.
• Life expectancy of \> 12 months.
• ECOG performance status ≤ 1
• Adequate bone marrow and organ function as defined below:
• WBC ≥ 1.5 K/cumm
• absolute neutrophil count ≥ 1.0 K/cumm
• platelets ≥ 50 K/cumm
• hemoglobin ≥ 8.0 g/dL
• total bilirubin ≤ 5.0 X institutional upper limit of normal
• AST/ALT ≤ 5.0 X institutional upper limit of normal
• creatinine ≤2.5 X institutional upper limit of normal OR creatinine clearance ≥ 30 mL/min by Cockcroft-Gault for patients with creatinine levels above institutional normal
• Note: labs can be repeated prior to chemo if needed.

You may not qualify if:

• Evidence of predominantly neuroendocrine (defined by \> 50% histology) tumor, pure neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma.
• 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.
• Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy.
• Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
• Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, and/or other functional abnormality that might 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. If needed and appropriate. the final determination related to study eligibility prior to the administration of the first vaccine will be documented by both the PI and Sub-Investigators in consultation with a specialist.
• 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. Premedication for chemotherapy does not apply to this criteria and may be administered as per SOC practice. Any patients receiving steroids should be discussed with the PI to determine if eligible.
• Pregnant and/or breastfeeding.
• Known HIV-positive status.
• History of positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hepatitis C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.
• Step 1 Eligibility: At Step 1 eligibility confirmation prior to vaccination, the above criteria must be met plus:
• Completed at least 4 months of neoadjuvant chemotherapy such as FOLFIRINOX, modified FOLFIRINOX, or gemcitabine + nab-paclitaxel. Dose modifications and/or delays in neoadjuvant chemotherapy may be made at the discretion of the treating physician
• Reimaging within 4 weeks of last dose of chemotherapy demonstrates no evidence of progressive disease. Patients who progress on mFOLFIRINOX and transition to gemcitabine + nab-paclitaxel may still be eligible for vaccine administration at discretion of PI and treating MD provided they do not show progression following completion of chemotherapy and the patient continues to be eligible for surgical resection. Patients who, in the opinion of the treating physician, require SBRT prior to surgery will receive vaccine after surgery regardless of randomization.
• \*\*Patients who progress or recur following neoadjuvant chemotherapy or who are otherwise unable to complete a surgical resection, but who still meet other Step 1 criteria, may still be eligible for vaccine administration with documented treating physician and PI approval.
• There is a 1 week washout prior to Day 1 of vaccine for patients on daily systemic steroids at doses exceeding 10 mg prednisone.

Sponsors & Collaborators

• The Foundation for Barnes-Jewish Hospital: collaborator
• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator
• Leidos: collaborator
• UNICO Foundation: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

poly ICLC

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• William E Gillanders, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 8, 2021
• Study Start: December 15, 2022
• Primary Completion: November 3, 2025
• Study Completion: November 3, 2025
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)