Personalized Cancer Vaccine for Bladder Cancer

Overseen By Russell Pachynski, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 10

Duration: 24 weeks

16 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or systemic steroids, you may need to stop them 30 days before enrolling. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the Personalized Cancer Vaccine (PCV) treatment for bladder cancer?

Research suggests that personalized peptide vaccines can boost the immune system's ability to fight bladder cancer, especially in patients who have not responded well to other treatments. Additionally, combining cancer vaccines with other therapies, like BCG, has shown increased immune responses and tumor regression in bladder cancer models. ^{1 2 3 4 5}

Is the personalized cancer vaccine safe for humans?

Studies on personalized peptide vaccines for bladder and other urological cancers have shown that they are generally safe and well-tolerated, with no severe adverse events reported. ^{2 4 5 6 7}

How is the Personalized Cancer Vaccine treatment different from other bladder cancer treatments?

The Personalized Cancer Vaccine (PCV) is unique because it is tailored to each patient's specific cancer profile, aiming to boost the body's immune response against the cancer. Unlike standard treatments, which are the same for all patients, this vaccine selects specific peptides (small proteins) that are most likely to trigger an immune response in the individual, potentially offering a more targeted and effective approach. ^{1 2 4 8 9}

What is the purpose of this trial?

This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.

Research Team

William E Gillanders, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for patients with solid tumors, specifically bladder cancer, who have tiny amounts of cancer left after treatment (molecular residual disease). Participants should be adults with a good performance status and must not have autoimmune diseases or be on immunosuppressive medications.

Inclusion Criteria

I have a ctDNA report from both a tumor tissue sample and a blood test.

My bladder cancer was completely removed by surgery.

My recent scans show no signs of cancer or spread.

Exclusion Criteria

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

Psychiatric illness or social situations that would limit compliance with study requirements

Known allergy or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive personalized cancer vaccines on Days 1, 4, 8, 15, 29, 57, 85, 113, 141, and 169, co-administered with poly-ICLC

24 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including recurrence-free survival and immune response

78 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Personalized Cancer Vaccine (PCV)

Trial Overview The study tests a personalized cancer vaccine made from synthetic peptides tailored to each patient's tumor, given alongside Poly ICLC. It also uses the Signatera assay to monitor response and includes Nivolumab as part of the treatment regimen.

Participant Groups

Group I: Cohort 1: Muscle Invasive Bladder Cancer (PCV) Experimental Treatment 3 Interventions

The schedule for vaccination will be Days 1, 4, 8, 15, 29, 57, 85, 113, 141, and 169. All study injections will be given intramuscularly and co-administered with poly-ICLC by a trained healthcare provider.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Findings from Research

The personalized peptide vaccine (PPV) was found to be safe and well tolerated in a phase I trial involving 10 patients with advanced urothelial carcinoma, with no major adverse effects reported.

Eight out of ten patients showed increased immune responses, and while clinical outcomes varied, those who responded to the treatment had significantly longer median progression-free survival (21 months) and overall survival (24 months) compared to the overall median survival rates of 3.0 and 8.9 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin. Matsumoto, K., Noguchi, M., Satoh, T., et al.[2016]

References

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

An Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy. [2016]

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

Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Identification of tumor antigens and immune landscapes for bladder urothelial carcinoma mRNA vaccine. [2023]

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

A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin. [2016]

5. England pubmed.ncbi.nlm.nih.gov

A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Personalized peptide vaccination as second-line treatment for metastatic upper tract urothelial carcinoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Personalized peptide vaccines and their relation to other therapies in urological cancer. [2021]

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

Immunotherapy for orthotopic murine bladder cancer using bacillus Calmette-Guerin recombinant protein Mpt-64. [2007]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Adjuvant Intravesical Bacillus Calmette-Guérin Treatment on Patients with High-Grade T1 Bladder Cancer. [2016]