KRAS Peptide Vaccine for Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Nilofer S. Azad

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

This Phase 1 study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine with poly-ICLC adjuvant for patients who have been identified to be at risk of developing pancreatic cancer.

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.

What data supports the idea that KRAS Peptide Vaccine for Pancreatic Cancer is an effective treatment?

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 response to the vaccine, and those with advanced cancer who responded to the vaccine lived longer, with a median survival of 148 days compared to 61 days for non-responders. Another study found that 85% of patients who had surgery and received the vaccine showed an immune response, with a 10-year survival rate of 20%, compared to 0% in non-vaccinated patients. This suggests that the vaccine may help improve survival rates and strengthen the immune system's response to cancer. ^{1 2 3 4 5}

What safety data exists for the KRAS peptide vaccine for pancreatic cancer?

The KRAS peptide vaccine has been evaluated in several studies for safety and efficacy in pancreatic cancer. In a clinical phase I/II trial, the vaccine was well tolerated in all patients, including those with advanced disease. The study involved intradermal injection of synthetic mutant ras peptides with granulocyte-macrophage colony-stimulating factor as an adjuvant. Additionally, long-term follow-up of patients who received the vaccine after surgical resection showed that the vaccine was safe and elicited long-term immune responses. These studies suggest that the KRAS peptide vaccine is safe for use in patients with pancreatic cancer. ^{2 3 4 6 7}

Is the KRAS peptide vaccine a promising treatment for pancreatic cancer?

Yes, the KRAS peptide vaccine is a promising treatment for pancreatic cancer. It targets specific mutations found in pancreatic cancer cells, helping the immune system recognize and attack the cancer. Studies show that it can improve survival rates and create long-lasting immune responses in patients, even those with advanced cancer. ^{2 3 4 6 7}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• KRAS peptide vaccine (Cancer 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.

Participant Groups

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).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Sidney Kimmel Comprehensive Cancer Center Baltimore, MD

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Lead Sponsor

Stand Up To Cancer Collaborator

References

1. England 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. [2020] Mutations in codon 12 of K-RAS are frequently found in pancreatic adenocarcinomas. T-cell responses specific for individual RAS mutations can be elicited in vitro by stimulation of peripheral blood mononuclear cells with synthetic peptides. Mutant ras peptides are therefore a candidate vaccine for specific immunotherapy in pancreatic carcinoma patients. When vaccinated with a synthetic ras peptide representing the K-RAS mutation in their tumours, a transient ras-specific T-cell response was induced in two of five patients treated. The vaccination protocol involved multiple infusions of large amounts of peptide-pulsed antigen-presenting-cells obtained by leucapheresis. These results indicate that specific T-cell responses against mutations uniquely harboured in tumour cells can be induced in cancer patients by vaccination.

2. United States 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. [2021] K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte-macrophage colony-stimulating factor. Forty-eight patients (10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide-specific immunity was induced in 25 of 43 (58%) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end-stage disease. Patients followed-up for longer periods showed evidence of induction of long-lived immunological memory against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras-specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients. Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non-responders (median survival 148 days vs. 61 days, respectively; p = 0.0002). Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients.

3. China pubmed.ncbi.nlm.nih.gov

[Anti-pancreatic cancer immune response induced by K-ras mutated peptide]. [2021] Since most tumor antigens are uncertain, the immunotherapy against tumors still lingers in clinical trials. Because k-ras proto-oncogene specifically expresses in pancreatic cancer cells with constant mutation site, it may be an ideal target for immunotherapy against pancreatic cancer. This study was to evaluate the feasibility of inducing immunotherapy on pancreatic cancer by K-ras mutated peptides, give experimental evidence to clinical individual therapy on pancreatic cancer.

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

Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. [2021] K-ras mutations are frequently found in adenocarcinomas of the pancreas and can elicit mutation-specific immune responses. Targeting the immune system against mutant Ras may thus influence the clinical course of the disease. Twenty-three patients who were vaccinated after surgical resection for pancreatic adenocarcinoma (22 pancreaticoduodenectomies, one distal resection), in two previous Phase I/II clinical trials, were followed for more than 10 years with respect to long-term immunological T-cell reactivity and survival. The vaccine was composed of long synthetic mutant ras peptides designed mainly to elicit T-helper responses. Seventeen of 20 evaluable patients (85%) responded immunologically to the vaccine. Median survival for all patients was 27.5 months and 28 months for immune responders. The 5-year survival was 22% and 29%, respectively. Strikingly, 10-year survival was 20% (four patients out of 20 evaluable) versus zero (0/87) in a cohort of nonvaccinated patient treated in the same period. Three patients mounted a memory response up to 9 years after vaccination. The present observation of long-term immune response together with 10-year survival following surgical resection indicates that K-ras vaccination may consolidate the effect of surgery and represent an adjuvant treatment option for the future.

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

Mutated Ras peptides as vaccines in immunotherapy of cancer. [2021] Mutations in codon 12 and 13 of K-RAS are frequently found in human cancer, including pancreatic- and colorectal adenocarcinomas. T cell responses specific for individual RAS mutations can be elicited in vitro by stimulation with synthetic peptides and in vivo following vaccination with antigen presenting cells pulsed ex vivo with synthetic peptides. The peptide-responding T cells are capable of responding to intact p21 ras, and can recognise and kill tumour cell lines and isolated tumour cells harbouring the corresponding RAS mutation. The responding cells can be of both CD4+ and CD8+ phenotype, and these T cell subsets recognise nested epitopes within the vaccine peptides. Mutant ras peptides are therefore possibly an important vaccine for specific immunotherapy in patients with pancreatic and colorectal carcinomas, and are currently being tested in vivo together with GM-CSF as an adjuvant in these cancer patients.

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

Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine. [2020] Codon 12 mutations of K-ras are frequent in pancreatic adenocarcinoma, and represent potential tumor-specific neoantigens. The objective of this study was to assess the safety and efficacy of immunizing patients with resected pancreatic cancer with a vaccine targeted against their tumor-specific K-ras mutation.

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

Immunoprevention of KRAS-driven lung adenocarcinoma by a multipeptide vaccine. [2019] Lung cancer remains the leading cause of cancer death worldwide. Mutations in KRAS are detected in up to 30% of lung cancer cases. No effective therapies specifically targeting mutant KRAS have been developed. Vaccination against KRAS mutants is one of the venues of active exploration. The present study evaluated both immunogenicity and antitumor efficacy of a newly formulated multipeptide vaccine targeting multiple epitopes of the KRAS molecule. The formulated vaccine contained top four peptides, which elicited the strongest immunologic response and showed 100% sequence homology between human and mouse. The multipeptide KRAS vaccine was tested in an inducible CCSP-TetO-KRASG12D mouse model, where the vaccine was administered prior to activating the mutant KRAS protein. The KRAS peptide vaccine exhibited striking efficacy, reducing tumor number and tumor burden by >80% when compared with adjuvant alone. Splenocytes collected from vaccinated animals showed a robust immunologic response to the immunizing peptides. Furthermore, in vitro stimulation of these splenocytes by the vaccinated peptides resulted in the secretion of cytokines indicative of Th1 responses but with minimal secretion of Th2-related cytokines. The multipeptide KRAS vaccine was immunogenic and efficacious in the primary prevention of KRAS-induced lung cancer, indicating that the approach potentially can be used to prevent other KRAS-driven cancers, either alone or in combination with other modalities.