Lung Cancer Vaccine for Lung Cancer Prevention and Recurrence
Recruiting in Palo Alto (17 mi)
Overseen byMary Reid, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Roswell Park Cancer Institute
Must not be taking: Immunosuppressants, Steroids
Disqualifiers: Uncontrolled illness, Cardiac arrhythmia, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This early phase I trial studies the side effects of a vaccine called CIMAvax-EGF and to see how well it works in preventing lung cancer from developing in patients at high risk for lung cancer or coming back (recurrence) in stage IB-IIIA non-small cell lung cancer survivors. In many cancers such as lung cancer, there is a protein receptor called EGFR (epidermal growth factor receptor) that is overexpressed within these cancers. Activation of EGFR has shown to lead to tumor growth and development. Previous studies have indicated that EGFR activation is present in the airways of cancer-free subjects as well. CIMAvax-EGF vaccine works by causing the body to make antibodies against EGF that is being produced that could be possibly driving the risk for developing cancer.
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, if you are using systemic immunosuppressant drugs like steroids, you must stop them at least 4 weeks before joining the study.
What data supports the effectiveness of the lung cancer vaccine treatment for lung cancer prevention and recurrence?
Research shows that the EGF-based vaccine, similar to the one being studied, has been effective in advanced non-small-cell lung cancer (NSCLC) by inducing an immune response that helps block cancer growth signals. Patients who developed a strong immune response to the vaccine lived longer than those who did not.
12345Is the lung cancer vaccine safe for humans?
The lung cancer vaccine, also known as CIMAvax-EGF or Hu-rhEGF-rP64k/Mont, has been tested in several clinical trials and is generally considered safe for humans. Common side effects include mild reactions at the injection site, fever, headache, and vomiting, but no significant toxicity has been reported.
12467How does the lung cancer vaccine differ from other treatments for lung cancer?
The lung cancer vaccine, CIMAvax-EGF, is unique because it targets the epidermal growth factor (EGF), a protein that helps cancer cells grow. By inducing the body to produce antibodies against EGF, it prevents EGF from activating its receptor on cancer cells, which can slow down or stop the growth and spread of the cancer. This approach is different from traditional treatments that directly target the cancer cells themselves.
13489Eligibility Criteria
This trial is for high-risk individuals or stage IB-IIIA non-small cell lung cancer survivors without current evidence of cancer. Participants must have a good performance status, agree to contraception if applicable, and not be pregnant. High-risk factors include moderate/severe COPD, family history of lung cancer, low BMI, pneumonia in the last 5 years, exposure to certain substances like asbestos or radon, recent smoking history with significant pack-years.Inclusion Criteria
I am at high risk for lung cancer due to factors like COPD, family history, low BMI, recent pneumonia, occupational exposure, or smoking history.
You must have enough platelets in your blood (at least 100 billion per liter).
Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
+5 more
Exclusion Criteria
It is not safe for me to undergo a bronchoscopy.
I have a condition that weakens my immune system, like HIV.
I am an adult capable of making decisions, not pregnant, and not incarcerated.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Loading Phase
Patients receive recombinant human EGF-rP64K/montanide ISA 51 vaccine intramuscularly at 0, 2, 4, and 6 weeks
6 weeks
4 visits (in-person)
Maintenance Phase
Patients receive recombinant human EGF-rP64K/montanide ISA 51 vaccine intramuscularly once every 4 weeks
Ongoing until disease progression or unacceptable toxicity
Monthly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
60 days
Participant Groups
The CIMAvax-EGF vaccine is being tested for its ability to prevent the development or recurrence of lung cancer by targeting a protein (EGFR) linked to tumor growth. The study includes questionnaires and quality-of-life assessments alongside the vaccine administration.
1Treatment groups
Experimental Treatment
Group I: Prevention (recombinant human EGF-rP64K/montanide ISA 51)Experimental Treatment3 Interventions
LOADING PHASE: Patients receive recombinant human EGF-rP64K/montanide ISA 51 vaccine IM at 0, 2, 4 and 6 weeks in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Patients receive recombinant human EGF-rP64K/montanide ISA 51 vaccine IM Q4W in the absence of disease progression or unacceptable toxicity.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Roswell Park Cancer InstituteBuffalo, NY
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Who Is Running the Clinical Trial?
Roswell Park Cancer InstituteLead Sponsor
References
Therapeutic cancer vaccine: phase I clinical tolerance study of Hu-rhEGF-rP64k/Mont in patients with newly diagnosed advanced non-small cell lung cancer. [2019]Hu-rhEGF-rP64k/Mont is a biotechnology product for the treatment of advanced non-small cell lung cancer (NSCLC). The vaccine induces a neutralizing antibody-mediated immune response, against the normal circulating self-protein antigen epidermal growth factor (EGF), which prevents its binding to and activation of the EGF receptor, inhibiting the transduction of the signals that drive cancer cell proliferation, survival and spread. This phase I study aimed to evaluate the safety and the immunological response of Hu-rhEGF-rP64k vaccine in NSCLC patients.
Treatment of NSCLC patients with an EGF-based cancer vaccine: report of a Phase I trial. [2020]Epidermal Growth Factor (EGF) promotes tumor cell proliferation and survival upon binding to its receptor. We have developed a new active specific immunotherapy based on EGF deprivation. In the present paper, we show the results of a Phase I trial in 43 patients with advanced non-small cell lung cancer (NSCLC) who received the EGF vaccine. Patients who had already received first line therapy were randomized to receive a single or double dose of the EGF vaccine, weekly for four weeks and monthly thereafter. No significant toxicity was seen after vaccination. Adverse events consisted primarily of fever, chills, nausea, vomiting and flushing. Fifteen patients (39%) developed a good antibody response (GAR) against EGF. The geometric mean of the antibody titer was higher in the double dose group. EGF concentration was quantified in serum. An inverse correlation between anti-EGF antibody titers and EGF concentration was seen after immunization. Vaccinated patients achieved median survival times of 8.23 months from randomization. Patients who received the double dose of treatment showed a trend toward increased survival in comparison with patients who received the single dose. GAR and patients in whom the serum EGF decreased below the 168 pg/ml cut-off point had a significantly better survival when compared to poor responders or patients in which the EGF levels were not considerably reduced. Our results confirm the immunogenicity of the EGF vaccine in the treatment of patients with advanced stage NSCLC. Antibody titers and serum EGF levels appear to correlate with patient survival.
CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer. [2019]Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial tumors and its role in the development of non-small-cell lung cancer (NSCLC) is widely documented. CIMAvax-EGF is a therapeutic cancer vaccine composed by recombinant EGF conjugated to a carrier protein and emulsified in Montanide ISA51. Vaccination induces antibodies against self-EGF that block EGF-EGFR interaction and inhibit EGFR phosphorylation. Five clinical trials were conducted to optimize vaccine formulation and schedule. Then, two randomized studies were completed in advanced NSCLC, where CIMAvax-EGF was administered after chemotherapy, as 'switch maintenance'. The vaccine was very well tolerated and the most frequent adverse events consisted of grade 1/2 injection site reactions, fever, headache, vomiting and chills. CIMAvax was immunogenic and EGF concentration was reduced after vaccination. Subjects receiving a minimum of 4 vaccine doses had a significant survival advantage. NSCLC patients with high EGF concentration at baseline had the largest benefit, comparable with best maintenance therapies.
Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. [2018]We show the result of a randomized phase II clinical trial with an epidermal growth factor (EGF)-based cancer vaccine in advanced non-small-cell lung cancer (NSCLC) patients, evaluating immunogenicity, safety, and effect on survival.
Therapeutic vaccination with epidermal growth factor (EGF) in advanced lung cancer: analysis of pooled data from three clinical trials. [2019]We have undertaken the analysis of pooled data from three pilot clinical trials of vaccination with Epidermal Growth Factor (EGF) in patients with advanced non small cell lung cancer (NSCLC), addressing particularly the issue of the relationship between immunization and survival. Eighty-three patients with advanced disease were included in three pilot clinical trials and vaccinated with the EGF Vaccine. The trials were designed to evaluate the immunogenicity and safety of the vaccine using different adjuvants, cyclophosphamide pretreatment or not, and different dosage levels of the vaccine. The vaccine elicited specific anti-EGF antibody titers in 83% of subjects, and 49% developed a good anti-EGF antibody response. The adjuvant, the vaccine dose, and cyclophosphamide pretreatment significantly influenced immunogenicity. Patients that seroconverted survived significantly longer than patients who did not. Good antibody responders survived significantly longer than poor responders. Pooled results from these trials confirm that vaccination with EGF is safe and immunogenic in advanced NSCLC patients. The association between good antibody responses and survival consistently appeared in every single trial independently of the specific trial designs. Although these were small pilot nonrandomized clinical trials not intended to confirm therapeutic effect, the survival of the pooled patient population was statistically greater compared with 163 control patients receiving standard treatment.
CIMAvax-EGF: A New Therapeutic Vaccine for Advanced Non-Small Cell Lung Cancer Patients. [2019]Lung cancer is the common fatal illness with the highest incidence and mortality globally. Epidermal growth factor receptor overexpression by tumor cells is associated with uncontrolled proliferation, angiogenesis, anti-apoptotic signals, metastization, and invasiveness. CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and Montanide ISA 51, as adjuvant. The vaccine is projected to induce antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF demonstrated to be safe and immunogenic in advanced non-small cell lung cancer (NSCLC) patients. The efficacy study was an open-label, multicentric Phase III clinical trial, which enrolled 405 advanced NSCLC patients. Patients with proven stage IIIB/IV NSCLC, who had completed four to six cycles of chemotherapy (CTP) were randomized to receive CIMAvax-EGF or best supportive care. CIMAvax-EGF resulted in a significantly larger overall survival in patients receiving at least four doses. High EGF concentration at baseline was a good predictive biomarker of the vaccine activity and a poor prognostic biomarker for the non-treated population. The proportion of CD8+CD28- cells, CD4 cells, and the CD4/CD8 ratio after first-line CTP was also associated with CIMAvax-EGF clinical benefit. After completing the Phase III, a Phase IV trial was done where the vaccine was administered in primary care units. Administering the vaccine at primary care institutions granted better access and treatment compliance. Safety was confirmed. Several clinical trials are currently ongoing to validate EGF as a predictive biomarker of CIMAvax-EGF efficacy.
Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an Epidermal Growth Factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients. [2021]The prognosis of patients with advanced non small cell lung (NSCLC) cancer remains dismal. Epidermal Growth Factor Receptor is over-expressed in many epithelial derived tumors and its role in the development and progression of NSCLC is widely documented. CimaVax-EGF is a therapeutic cancer vaccine composed by human recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein, P64K from Neisseria Meningitides. The vaccine is intended to induce antibodies against self EGF that would block EGF-EGFR interaction. CimaVax-EGF has been evaluated so far in more than 1000 advanced NSCLC patients, as second line therapy. Two separate studies were compared to assess the impact of high dose vaccination at multiple anatomic sites in terms of immunogenicity, safety and preliminary efficacy in stage IIIb/IV NSCLC patients. In both clinical trials, patients started vaccination 1 month after finishing first line chemotherapy. Vaccination at 4 sites with 2.4 mg of EGF (high dose) was very safe. The most frequent adverse events were grade 1 or 2 injection site reactions, fever, headache and vomiting. Patients had a trend toward higher antibody response. The percent of very good responders significantly augmented and there was a faster decrease of circulating EGF. All vaccinated patients and those classified as good responders immunized with high dose at 4 sites, had a large tendency to improved survival.
CIMAvax-EGF: Toward long-term survival of advanced NSCLC. [2018]Lung cancer remains one of the leading causes of cancer-related deaths. Non-small cell lung cancer (NSCLC) is the most common histologic type of lung cancer. Medical and scientific progress has led to longer survival in an increasing number of patients suffering from cancer. Concerning patients with advanced NSCLC, there is a subgroup with long-term survival. The human epidermal growth factor receptor (EGFR) family plays a key role in tumor development. This cluster of genes is associated with augmented angiogenesis and enhanced proliferation, survival, and migration of tumor cells. The CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and the Montanide ISA 51, as adjuvant. The vaccine induces antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF has been demonstrated to be safe and immunogenic in advanced NSCLC patients. Here we summarize the current knowledge of the mechanism of action of CIMAvax-EGF, highlighting the impact of this anti-EGF-based vaccine on the long-term survival of advanced NSCLC patients.
A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients. [2018]EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction.