Personalized Cancer Vaccine for Pancreatic and Colorectal Cancer

Overseen By Michael Overman

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiretrovirals, Corticosteroids, Immunosuppressives, others

Disqualifiers: HIV/AIDS, Brain metastases, Autoimmune, others

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

Compensation: Varies

Number of Visits: 14

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new personalized cancer vaccine made from a patient's own tumor cells and blood. The goal is to assess the vaccine's safety and determine the best delivery method for individuals with advanced pancreatic or colorectal cancer that has spread and cannot be cured with current treatments. Different groups in the trial test combinations of the vaccine with other treatments. Patients with metastatic pancreatic or colorectal cancer, who can undergo surgery to remove tumors and have sufficient tumor tissue available, might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or have had chemotherapy or radiotherapy within 2 weeks before starting the trial treatment.

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

Research has shown that personalized cancer vaccines, such as synthetic tumor-associated peptide vaccine therapy, are being tested for safety and effectiveness in individuals with advanced pancreatic or colorectal cancer. Early results suggest these vaccines are generally safe, with most participants experiencing only mild side effects, like soreness at the injection site or mild flu-like symptoms.

Studies indicate that therapy with imiquimod is relatively safe. Imiquimod, a cream applied to the skin, helps boost the immune system and is often used in other treatments. It is known to cause mostly mild skin reactions, such as redness or itching at the application site.

When combined with pembrolizumab, a drug already approved for other cancers, the vaccine has demonstrated manageable safety levels. Pembrolizumab can cause immune-related side effects, such as tiredness or a skin rash, but these are usually mild.

Lastly, when the vaccine is used with sotigalimab, an agent that stimulates the immune system, safety data from other studies suggest that side effects are similar and generally mild.

Because this trial is in an early phase, the main goal is to determine the best dose and closely monitor for any side effects. Participants receive careful monitoring to ensure their safety throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these personalized cancer vaccines for pancreatic and colorectal cancer because they represent a groundbreaking approach to cancer treatment. Unlike traditional therapies like chemotherapy and radiation, which target cancer cells broadly, these vaccines are tailored to the unique tumor-associated peptides of each patient, offering a more targeted attack on the cancer. Additionally, when combined with agents like pembrolizumab, imiquimod, and sotigalimab, these vaccines potentially enhance the immune system's response, aiming for a more robust and durable fight against cancer. This innovative strategy could lead to more effective treatments with fewer side effects compared to current standard care options.

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

Research shows that personalized peptide vaccines might help fight cancer by using parts of the tumor to create a targeted attack. Studies have found that these vaccines can train the immune system to recognize and attack tumor cells in pancreatic and colorectal cancer. In this trial, participants in different cohorts will receive various combinations of treatments. Cohort A will receive the personalized vaccine with imiquimod. Cohort B will receive the personalized vaccine with imiquimod and pembrolizumab. Cohorts C and D will receive the personalized vaccine with imiquimod, pembrolizumab, and APX005M. Early results suggest that combining these vaccines with other treatments, like imiquimod and pembrolizumab, might lead to a stronger immune response against cancer. Pembrolizumab is already known to help the immune system fight cancer, which could enhance the vaccine's effectiveness. Overall, these methods aim to stop tumors from growing or even shrink them by customizing the treatment to each patient's specific cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Michael J Overman, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced pancreatic or colorectal cancer who have a life expectancy of more than 6 months and can provide tumor tissue. They must have had at least one line of standard chemotherapy, be able to use birth control, and not be pregnant or breastfeeding. Specific criteria apply for different cohorts within the study.

Inclusion Criteria

Patients must demonstrate an ability to understand and the willingness to sign a written informed consent document

I have metastatic colorectal cancer and have had or will have surgery to remove the cancer spread.

I have finished all my planned additional cancer treatments.

Exclusion Criteria

I have another cancer that is getting worse or needs treatment.

I haven't had chemotherapy or radiotherapy in the last 2 weeks and have recovered from any side effects.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive personalized synthetic tumor-associated peptide vaccine therapy with imiquimod, pembrolizumab, and/or sotigalimab, along with CT or MRI scans at specified intervals.

24 weeks

11 visits (in-person) for vaccine administration and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including assessments of overall survival and recurrence-free survival.

6 months

Regular follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Synthetic Tumor-Associated Peptide Vaccine Therapy

Trial Overview The trial is testing a personalized peptide vaccine made from patients' own tumor cells and blood, alongside other treatments like Pembrolizumab and Sotigalimab. It aims to see how well these work as biological therapies against advanced cancers that are hard to treat.

How Is the Trial Designed?

Group I: Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M) Experimental Treatment 6 Interventions

Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.

Group II: Cohort B (personalized vaccine, imiquimod, pembrolizumab) Experimental Treatment 5 Interventions

Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.

Group III: Cohort A (personalized vaccine, imiquimod) Experimental Treatment 4 Interventions

Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 pilot study involving 5 patients with advanced pancreatic cancer, a synthetic ras peptide vaccine was well tolerated and did not cause any side effects, even when an immune response was observed.

The treatment successfully induced an immune response against the ras peptide in 2 out of the 5 patients, suggesting that this vaccination approach may be a safe and promising option for stimulating the immune system in advanced cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study. Gjertsen, MK., Bakka, A., Breivik, J., et al.[2020]

In a study of 309 pancreatic cancer patients undergoing personalized peptide vaccination (PPV), those who experienced 'immune boosting' (a significant increase in IgG levels post-vaccination) had longer survival rates, indicating that immune response plays a crucial role in treatment efficacy.

Pre-vaccination factors such as high C-reactive protein levels, advanced disease stage, and previous chemotherapy courses were linked to reduced clinical benefits from PPV, suggesting that inflammation and disease progression impact the effectiveness of this personalized treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer. Uchino, Y., Muroya, D., Yoshitomi, M., et al.[2021]

In a study of 500 advanced cancer patients receiving personalized peptide vaccinations, only 6 vaccine-related severe adverse events (SAEs) were recorded, indicating a low incidence of serious side effects associated with the treatment.

The majority of SAEs were linked to cancer progression rather than the vaccine itself, but the 6 vaccine-related SAEs involved significant immune responses, highlighting the need for physicians to monitor for these rare occurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of severe adverse events after peptide vaccination for advanced cancer patients: Analysis of 500 cases. Yoshida, K., Noguchi, M., Mine, T., et al.[2010]

A phase I trial of a multiantigen-specific T-cell therapy using patients' own nonengineered T cells showed safety and potential effectiveness in treating advanced pancreatic cancer.

Patients receiving this therapy, alongside chemotherapy, exhibited responses, suggesting that this approach could enhance treatment outcomes for those with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy Shows Promise in Pancreatic Cancer. [2020]

A personalized four-peptide cancer vaccine targeting specific mutations in a pancreatic tumor led to a diverse and long-lasting immune response in a 62-year-old patient, contributing to a complete remission that has lasted for 4 years.

The study demonstrated that the vaccine elicited a significant T-cell response against three of the four peptides, with evidence of T-cell persistence over time, suggesting the potential for this approach to enhance tumor immunity and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report. Sonntag, K., Hashimoto, H., Eyrich, M., et al.[2019]

Immune checkpoint inhibitors have shown promise in treating colorectal cancer (CRC) patients with hyper-mutated tumors, indicating a significant role for immune therapy in CRC management.

Personalized neoantigen-based peptide vaccines, particularly when combined with immune-stimulatory treatments, have demonstrated promising results without severe adverse events, suggesting they could become a key component of precision medicine for CRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens. Wagner, S., Mullins, CS., Linnebacher, M.[2020]

The p53 synthetic long peptide (p53-SLP) vaccine was found to be safe for use in patients with metastatic colorectal cancer, with limited toxicity primarily at the vaccination site.

The vaccine successfully induced p53-specific T-cell responses in 9 out of 10 patients, with some T-cell reactivity persisting for at least 6 months, indicating its potential effectiveness as an immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Speetjens, FM., Kuppen, PJ., Welters, MJ., et al.[2021]

In a phase I study involving 11 pancreatic cancer patients, personalized peptide vaccination was generally well tolerated, with some inflammatory reactions noted, indicating a manageable safety profile for this treatment approach.

The study showed promising immunological responses, with 4 out of 8 patients exhibiting increased immune responses post-vaccination, and patients receiving more than 3 vaccinations had a 6-month survival rate of 80%, suggesting potential efficacy for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological evaluation of personalized peptide vaccination for patients with pancreatic cancer. Yamamoto, K., Mine, T., Katagiri, K., et al.[2011]

Mutations in the K-RAS gene are common in pancreatic cancer, and targeting these mutations with synthetic peptides can stimulate T-cell responses in patients.

In a small study of five patients, two showed a transient T-cell response after being vaccinated with a synthetic peptide representing their specific K-RAS mutation, suggesting that this approach could be a promising avenue for immunotherapy in pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation. Gjertsen, MK., Bakka, A., Breivik, J., et al.[2020]

Citations

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NCT02600949 | Personalized Peptide Vaccine in Treating ... This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer that has ...

2. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2014-1029.html

Pilot Study of The Feasibility And Safety Of A Personalized ... This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12299967/

Research and Clinical Progress of Therapeutic Tumor Vaccines Synthetic tumor-associated peptide, /, Pancreatic cancer. Colorectal cancer ... Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2016-00015

Personalized Peptide Vaccine in Treating Patients with ... This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer that has ...

5. trialx.com trialx.com/clinical-trials/listings/272850/personalized-peptide-vaccine-in-treating-patients-with-advanced-pancreatic-cancer-or-colorectal-cancer/

Personalized Peptide Vaccine in Treating Patients With ... This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer

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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) ...