Neoantigen Vaccine for Pancreatic Cancer

No longer recruiting at 1 trial location

Overseen By William E Gillanders, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Neuroendocrine tumor, Autoimmune disease, HIV, Hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 14

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine for people with pancreatic cancer. Researchers aim to determine if the Neoantigen synthetic long peptide vaccine is safe and effective when administered after standard chemotherapy, either before or after surgery. The vaccine targets specific proteins in cancer cells and is given with a booster to enhance the immune system. Individuals with newly diagnosed pancreatic cancer, undergoing chemotherapy, and who have not yet had surgery might be suitable candidates for this trial. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a 1-week period without taking daily systemic steroids if you are on doses exceeding 10 mg of prednisone before starting the vaccine.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a 1-week period without taking systemic steroids if you are on doses exceeding 10 mg of prednisone per day. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that neoantigen vaccines, like the one tested for pancreatic cancer, are generally safe. Early studies found that these vaccines are usually well-tolerated, with most side effects being mild.

For example, patients who received neoantigen synthetic long peptide vaccines mostly experienced mild reactions, such as soreness at the injection site or slight tiredness. These vaccines aim to help the body's immune system fight cancer cells.

Poly-ICLC, another ingredient in these vaccines, has also been researched. It is often added to enhance the vaccine's effectiveness. Studies have shown that poly-ICLC is generally safe, with mild side effects like flu-like symptoms that usually resolve on their own.

This is a phase 1 trial, which primarily checks for safety, but earlier studies of similar vaccines suggest they are well-tolerated. Always discuss any concerns with a doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the neoantigen vaccine for pancreatic cancer because it offers a personalized approach by using fragments of proteins, or neoantigens, that are unique to each patient's tumor. Unlike standard treatments for pancreatic cancer like chemotherapy and radiation, which target both healthy and cancerous cells, this vaccine is designed to activate the immune system to specifically attack cancer cells. Another distinctive feature is its administration alongside poly-ICLC, an immune system booster, which is given intramuscularly to enhance the vaccine's effectiveness. By focusing on the unique mutations present in each patient's cancer, this treatment aims to improve precision and potentially lead to better outcomes.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that neoantigen synthetic long peptide vaccines can help cancer patients live longer. These vaccines target specific proteins on cancer cells, aiding the immune system in recognizing and attacking them. Early studies in pancreatic cancer demonstrated that these vaccines are safe and can trigger a strong immune response. In this trial, participants will receive the neoantigen vaccine either after neoadjuvant chemotherapy and surgery or after neoadjuvant chemotherapy but before surgery. The vaccines are often used with Poly-ICLC, a substance that boosts the body's immune response. Poly-ICLC has effectively slowed cancer growth by activating certain parts of the immune system. Overall, these treatments show promise in helping the immune system fight pancreatic cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

William E Gillanders, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with newly diagnosed, treatable pancreatic adenocarcinoma who are set for neoadjuvant chemotherapy and surgery. They must have a life expectancy over 12 months, good organ function, and agree to use two forms of contraception. Excluded are those with other cancers within the last 3 years (except certain skin cancers), known allergies to vaccines, HIV or hepatitis B/C infections, autoimmune diseases requiring immunosuppression, or any condition that limits study compliance.

Inclusion Criteria

I am suspected to have pancreatic cancer and will confirm it with a biopsy before treatment.

I have a new diagnosis of pancreatic cancer that hasn't been treated yet.

Able to understand and willing to sign an IRB approved written informed consent document

Exclusion Criteria

Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy

I have tested positive for Hepatitis B or C.

I do not have any major health issues that could make participating unsafe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive institutional standard of care chemotherapy prior to vaccine administration

Varies

Vaccine Administration (Arm 1)

Neoantigen peptide vaccine administered after neoadjuvant chemotherapy and surgery

Approximately 11 weeks

7 visits (in-person)

Vaccine Administration (Arm 2)

Neoantigen peptide vaccine administered after neoadjuvant chemotherapy but before surgery

Approximately 11 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Optional immune monitoring at 1 and 2 years after last vaccine administration

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Neoantigen synthetic long peptide vaccine
• Optimized neoantigen synthetic long peptide vaccine
• Poly-ICLC

Trial Overview This trial tests an optimized neoantigen synthetic long peptide vaccine given alongside poly-ICLC in patients with pancreatic cancer. Participants will be randomly assigned to receive this vaccine either after neoadjuvant chemotherapy but before surgery (Arm 2) or following both chemo and surgery (Arm 1).

How Is the Trial Designed?

Group I: Arm 2: Vaccine given after neoadjuvant chemotherapy but before surgery Experimental Treatment 2 Interventions

* 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.

Group II: Arm 1: Vaccine given after neoadjuvant chemotherapy and surgery Experimental Treatment 2 Interventions

* 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.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Leidos

Collaborator

Trials

1

Recruited

30+

UNICO Foundation

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

Pancreatic tumors are highly resistant to chemotherapy and are often diagnosed at advanced stages, leading to limited treatment options for patients.

Despite decades of research into vaccine therapies for pancreatic cancer, recent reviews indicate that none have successfully improved clinical outcomes, highlighting the ongoing challenges in developing effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis? Mizuguchi, T., Torigoe, T., Satomi, F., et al.[2023]

In a phase I trial involving 16 patients with pancreatic ductal adenocarcinoma (PDAC), the individualized neoantigen vaccine autogene cevumeran was found to be tolerable and successfully induced high levels of neoantigen-specific T cells in half of the patients, suggesting a promising immune response.

Patients who developed vaccine-expanded T cells had significantly longer recurrence-free survival (not reached) compared to those who did not, indicating that the vaccine may help delay the recurrence of PDAC when combined with atezolizumab and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Rojas, LA., Sethna, Z., Soares, KC., et al.[2023]

The neoantigen-targeted vaccine PancVAX, developed using whole-exome and RNA sequencing, effectively activated T cells against pancreatic cancer in mice, leading to temporary tumor regression.

When combined with checkpoint modulators (anti-PD-1 and OX40 antibodies), PancVAX not only enhanced tumor regression but also promoted T cell memory, suggesting a potential for long-lasting immunity against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer. Kinkead, HL., Hopkins, A., Lutz, E., et al.[2022]

Polyinosinic:polycytidylic acid (poly-ICLC) has shown potential as an effective adjuvant in cancer vaccines, enhancing anti-tumor immune responses and aiding in tumor elimination in both animal models and human patients.

Current research is actively exploring poly-ICLC-containing cancer vaccines in ongoing clinical trials, suggesting it may play a significant role in future cancer immunotherapy approvals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. Ammi, R., De Waele, J., Willemen, Y., et al.[2022]

A personalized neoantigen nanovaccine combined with anti-PD-1 antibody treatment led to a significant clinical benefit in an advanced pancreatic cancer patient, resulting in an overall survival of 10.5 months after treatment.

The treatment successfully induced a robust T cell response against multiple vaccine peptides, indicating that this approach may effectively enhance immune responses in controlling progressive metastatic pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report. Shao, J., Liu, Q., Shen, J., et al.[2023]

Synthetic long peptides (SLP) derived from carcinoembryonic antigen can effectively induce strong T cell and antibody responses in mice, highlighting their potential as a vaccine for chronic infections and tumors.

However, repeated vaccinations with SLP in saline led to anaphylaxis, indicating a safety concern; using a slow-release vehicle (IFA) with lower doses prevented this adverse reaction, emphasizing the importance of safe administration methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IgG-mediated anaphylaxis to a synthetic long peptide vaccine containing a B cell epitope can be avoided by slow-release formulation. Quakkelaar, ED., Fransen, MF., van Maren, WW., et al.[2014]

In a study of 23 patients with pancreatic adenocarcinoma who received a K-ras vaccine after surgery, 85% showed an immune response, suggesting the vaccine effectively stimulates the immune system against cancer.

The median survival for vaccinated patients was 27.5 months, with a notable 10-year survival rate of 20%, compared to 0% in non-vaccinated patients, indicating that K-ras vaccination may enhance long-term survival outcomes post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Wedén, S., Klemp, M., Gladhaug, IP., et al.[2021]

Neoantigen vaccines, particularly those using long synthetic peptides derived from tumor mutations, show promise in improving tumor-specificity and reducing side effects compared to traditional cancer vaccines.

These long peptides can potentially enhance immune responses by overcoming immune tolerance, leading to activation of both CD4+ and CD8+ T cells, which are crucial for effective cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized neoantigen vaccination with synthetic long peptides: recent advances and future perspectives. Chen, X., Yang, J., Wang, L., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8414362/

A Neoantigen-Based Peptide Vaccine for Patients With ... Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients' overall survival (OS) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05111353?term=AREA%5BConditionSearch%5D(Pancreatic%20Cancer)%20AND%20AREA%5BBasicSearch%5D(neoadjuvant)%20AND%20AREA%5BOverallStatus%5D(RECRUITING%20OR%20ACTIVE_NOT_RECRUITING)&rank=3

NCT05111353 | Neoantigen Vaccines in Pancreatic ... This is a randomized phase 1 clinical trial to evaluate the safety of an optimized neoantigen synthetic long peptide (SLP) vaccines in pancreatic cancer ...

3. siteman.wustl.edu siteman.wustl.edu/research/spore-pancreatic-cancer/project-2/

Mechanisms of Resistance to Neoantigen Vaccines to PDAC Our initial clinical experience targeting neoantigens in pancreatic cancer confirmed that neoantigen DNA and synthetic long peptide vaccines are capable of ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0092867425006853

A multi-adjuvant personal neoantigen vaccine generates ... Personalized neoantigen-targeting vaccines have demonstrated great promise; however, improved immunogenicity is still needed. Since antigen availability and ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/neoantigen-vaccine-pancreatic-kidney-cancer

Neoantigen Vaccines Keep Kidney, Pancreatic Cancer at ... New immune-based treatments for kidney and pancreatic cancer have shown promising results in two small clinical trials.

6. genomemedicine.biomedcentral.com genomemedicine.biomedcentral.com/articles/10.1186/s13073-024-01388-3

Neoantigen DNA vaccines are safe, feasible, and induce ... Our study demonstrates neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses.