Neoantigen Vaccine for Pancreatic Cancer

Overseen by William E Gillanders, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Washington University School of Medicine

Must be taking: Neoadjuvant chemotherapy

Must not be taking: Immunosuppressants, corticosteroids

Disqualifiers: Neuroendocrine tumor, other malignancy, others

Stay on Your Current Meds

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the Neoantigen Vaccine for Pancreatic Cancer treatment?

Research shows that personalized neoantigen vaccines can stimulate the immune system to attack pancreatic cancer cells, leading to longer survival times in some patients. In one study, patients with vaccine-induced immune responses had longer recurrence-free survival, and another study showed that combining the vaccine with other treatments led to tumor regression in mice. ^{1 2 3 4 5}

Is the neoantigen vaccine for pancreatic cancer safe for humans?

The neoantigen vaccine, including its components like Poly-ICLC, has been studied in humans and found to be generally tolerable, with some studies showing it enhances immune responses against tumors. However, there have been instances of allergic reactions in animal studies, suggesting the need for careful administration. ^{1 2 4 6 7}

How does the neoantigen vaccine treatment for pancreatic cancer differ from other treatments?

The neoantigen vaccine for pancreatic cancer is unique because it is personalized, using specific mutations from a patient's tumor to create a vaccine that stimulates the immune system to target cancer cells. This approach is different from standard treatments as it aims to enhance the body's own immune response to fight the cancer, potentially leading to longer recurrence-free survival. ^{1 2 4 5 8}

Research Team

William E Gillanders, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

Treatment Details

Interventions

• Neoantigen synthetic long peptide vaccine (Cancer Vaccine)
• Optimized neoantigen synthetic long peptide vaccine (Cancer Vaccine)
• Poly-ICLC (Immunostimulant)

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).

Participant Groups

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+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Leidos

Collaborator

Trials

1

Recruited

30+

UNICO Foundation

Collaborator

Trials

1

Recruited

30+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Poly(I:C) as cancer vaccine adjuvant: knocking on the door of medical breakthroughs. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report. [2023]

6. Australia pubmed.ncbi.nlm.nih.gov

Personalized neoantigen vaccination with synthetic long peptides: recent advances and future perspectives. [2021]

7. United States 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. [2014]

8. Japan pubmed.ncbi.nlm.nih.gov

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis? [2023]