KRAS Peptide Vaccine for Pancreatic Cancer

Overseen By Colleen Apostol, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Corticosteroids, Immunosuppressants, Monoclonal antibodies, others

Disqualifiers: HIV, Hepatitis B/C, Metastatic cancer, 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: 1

Duration: 17 weeks

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new vaccine designed to prevent pancreatic cancer in high-risk individuals. Researchers aim to ensure the vaccine's safety and observe the immune system's response. Two main groups participate: one includes individuals with family histories or genetic factors linked to pancreatic cancer, and the other includes those with specific types of pancreatic cysts. Those with a family history of pancreatic cancer, certain genetic mutations, or high-risk pancreatic cysts might find this trial suitable. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot take systemic or topical corticosteroids, immunosuppressive agents, or any investigational devices within 4 weeks before the first dose of the study drug. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that the KRAS peptide vaccine is likely to be safe for humans?

Research has shown that the KRAS peptide vaccine is generally safe for patients. In one study, about 58% of patients who received the vaccine had an immune response, indicating that the treatment can enhance the body's defenses without causing serious harm. The vaccine has been tested in patients with pancreatic and colorectal cancers and has proven safe for these groups.

Although this trial is in its early stages, studies typically prioritize safety. Researchers are closely monitoring for any side effects. So far, the data suggests that the vaccine is safe for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The KRAS peptide vaccine is unique because it targets specific KRAS mutations often found in pancreatic cancer. Unlike traditional treatments like chemotherapy and surgery, which aim to remove or kill cancer cells broadly, this vaccine is designed to stimulate the immune system to recognize and attack cells with these mutations. Researchers are excited about this treatment because it represents a personalized approach, potentially leading to more effective and less invasive options for those at high risk of developing pancreatic cancer. By focusing on the underlying genetic changes, the vaccine could offer a new level of precision in cancer prevention and treatment.

What evidence suggests that the KRAS peptide vaccine might be an effective treatment for pancreatic cancer?

Research has shown that the KRAS peptide vaccine, which participants in this trial may receive, could help treat pancreatic cancer. In earlier studies, this vaccine strengthened the immune system, enabling it to produce cells that fight cancer. Specifically, patients experienced a 12.75-fold increase in T cell responses, crucial for attacking cancer cells. The vaccine has also proven safe and shows early signs of effectiveness, particularly for those with minimal cancer remaining after treatment. Although more research is needed, these early results are promising for those at risk of developing pancreatic cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Nilofer S. Azad

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

This trial is for adults at high risk of developing pancreatic cancer due to genetic mutations or family history. Participants must have a documented pancreatic abnormality and adequate organ function. Women of childbearing potential and men must follow contraceptive guidelines. Exclusions include pregnancy, breastfeeding, major surgery, infections like HIV or hepatitis B/C, immunodeficiency, recent receipt of vaccines or corticosteroids.

Inclusion Criteria

I carry a gene mutation linked to a high risk of pancreatic cancer.

I am at high risk for pancreatic cancer due to my family history.

My organ and bone marrow functions meet the required levels for the study.

Exclusion Criteria

Are pregnant or breastfeeding

I am infected with HIV or hepatitis B or C.

I do not have any severe illnesses that my doctors are still trying to get under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive the KRAS peptide vaccine with poly-ICLC adjuvant

17 weeks

Multiple visits for vaccination and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Annual follow-up visits

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• KRAS peptide vaccine

Trial Overview The study tests the safety and immune response to a KRAS peptide vaccine with poly-ICLC adjuvant in individuals who are genetically predisposed to pancreatic cancer. It's an early-phase trial designed to see if this vaccine can potentially prevent the development of cancer in those at high risk.

How Is the Trial Designed?

Group I: Cohort B: Patients must have evidence of a pancreatic cystic neoplasm Experimental Treatment 1 Intervention

Patients must have clinical, radiographic, or histologic evidence of a pancreatic cystic neoplasm with high-risk features warranting surgical resection per the discretion of the treating hepatobiliary surgeon. In addition, cyst fluid analysis must demonstrate the presence of one of the six KRAS mutations included in the study vaccine. Germline mutation testing or a positive family history of pancreatic cancer is not required for enrollment in Cohort B.

Group II: Cohort A: Patients at high risk of developing pancreatic cancer. Experimental Treatment 1 Intervention

Patients will include those who have undergone pancreatic imaging with MRI or CT or EUS and found to have one or more pancreatic imaging abnormalities such as a pancreatic cyst consistent with an intraductal papillary mucinous neoplasm (IPMN) or parenchymal changes consistent with pancreatic intraepithelial neoplasia (PanIN). additionally patients with: 1. familial pancreatic cancer relatives 2. germline mutation carriers with an estimated lifetime risk of pancreatic cancer of \~10% or higher 3. germline mutation carriers with an estimated lifetime risk of pancreatic cancer of \~5%, all detailed in Section 3.1.1. These patients must also (as defined in Section 3.1.2).

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

In a phase I/II trial involving 48 patients with pancreatic adenocarcinoma, a vaccine using synthetic mutant ras peptides successfully induced an immune response in 58% of evaluable patients, demonstrating its potential effectiveness even in advanced disease stages.

Patients who developed an immune response to the vaccine had a significantly longer median survival (148 days) compared to non-responders (61 days), suggesting that the vaccine may provide clinical benefits for patients with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Gjertsen, MK., Buanes, T., Rosseland, AR., et al.[2021]

The multipeptide vaccine targeting KRAS mutations demonstrated over 80% reduction in tumor number and burden in a mouse model, indicating strong antitumor efficacy before the mutant KRAS protein was activated.

The vaccine elicited a robust immune response characterized by Th1 cytokine secretion, suggesting it could be an effective preventive strategy against KRAS-driven lung cancer and potentially other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoprevention of KRAS-driven lung adenocarcinoma by a multipeptide vaccine. Pan, J., Zhang, Q., Sei, S., et al.[2019]

The K-ras peptide vaccine for patients with resected pancreatic cancer was found to be safe, with no severe toxicities reported, although mild erythema at the injection site was common (94%).

Out of 24 vaccinated patients, only 11% showed a specific immune response to the K-ras mutation, and while median overall survival was 20.3 months, the vaccine's efficacy remains unproven, suggesting a need for more immunogenic vaccine strategies in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine. Abou-Alfa, GK., Chapman, PB., Feilchenfeldt, J., et al.[2020]

T cell responses targeting specific K-RAS mutations can be effectively generated through vaccination with synthetic peptides, showing potential for immunotherapy in pancreatic and colorectal cancers.

These T cells can recognize and kill tumor cells with the corresponding RAS mutations, and are currently being tested in combination with GM-CSF to enhance their effectiveness in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutated Ras peptides as vaccines in immunotherapy of cancer. Gjertsen, MK., Gaudernack, G.[2021]

The study identified a specific mutation in the k-ras oncogene in pancreatic cancer cells, which can be targeted for immunotherapy, showing promise for personalized treatment.

Dendritic cells pulsed with synthesized k-ras mutated peptides successfully induced cytotoxic T cells that effectively killed pancreatic cancer cells, suggesting a potential new approach for immunotherapy against this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-pancreatic cancer immune response induced by K-ras mutated peptide]. He, Y., Yang, B., Ruan, CG.[2021]

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

1. nature.com nature.com/articles/s41591-025-03876-4

Lymph node-targeted, mKRAS-specific amphiphile vaccine ... T cell responses above the median 12.75-fold increase from baseline significantly correlated with improved tumor biomarker response and relapse- ...

2. mskcc.org mskcc.org/news/vaccine-targeting-kras-in-pancreatic-and-colorectal-cancer-shows-promise

Vaccine Targeting KRAS in Pancreatic and Colorectal ... The results demonstrated this vaccine is safe and stimulates the patient's immune system to create cancer-fighting cells. At an average of 20 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12056101/

the promise of mutant KRAS-specific vaccines - PubMed Central The off-the-shelf ELI-002 vaccine has demonstrated safety and preliminary efficacy in MRD+ pancreatic cancer and CRC which makes it an ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05013216

NCT05013216 | Mutant KRAS -Targeted Long Peptide ... This study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with poly-ICLC adjuvant.

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.TPS2699

A phase I study of a pooled synthetic long peptide mutant ... This is a single-arm, open-label phase I trial evaluating mKRAS vaccine in patients with pancreatic cystic neoplasms at risk for developing PDAC and scheduled ...

6. withpower.com withpower.com/trial/phase-1-pancreatic-neoplasms-11-2021-19557

KRAS Peptide Vaccine for Pancreatic Cancer The available research shows that the KRAS Peptide Vaccine can be effective for pancreatic cancer patients. In one study, 58% of patients developed an immune ...