Clinical Study of Neoantigen Vaccine Combined With Targeted Drugs in the Treatment of Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Neoantigen vaccine is a new field of research in tumor immunotherapy, and some studies have been conducted with success on Melanoma and glioblastoma. Nearly 80% of lung cancers are diagnosed in an advanced stage (IIIB, and IV) and EGFR mutant non-small cell lung cancer will be resistant after targeted drug treatment. Neoantigen vaccine is a new treatment method for lung cancer, especially for patients with drug resistance.

Detailed Description
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This is a phase I clinical study of individualized neoantigen peptide vaccine combined with targeted drugs in the treatment of EGFR mutant non-small cell lung cancer aimed to evaluated the safety and immune response of the neoantigen vaccine treatment.

Official Title
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Clinical Study of Personalized Neoantigen Peptide Vaccine Combined With Targeted Drugs in the Treatment of Non-small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: neoantigen vaccine + EGFR-TKI
* Drug: neoantigen vaccine + anti-angioge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced or metastatic non-small-cell lung cancer (stage III or stage IV). With EGFR-TKI sensitive mutations and no T790M. First generation EGFR-TKI treatment is in progress, the treatment time is 5-6 months and there is no disease progression. Patients aged 18 to 85 Life expectancy of at least 3 months. ECOG Performance Status 0 to 3. No previous immunotherapy, including anti-PD-1/PD-L1 or co-suppressive T cell receptor drug therapy, peptide / mRNA neoantigen immunotherapy and cell therapy. Ability to follow research and follow-up procedures. Able to understand and willing to sign an IRB approved written informed consent document. Exclusion Criteria: Pregnant and/or breastfeeding. With active, known or suspected autoimmune diseases or other concurrent immune system diseases. Receive systemic cytotoxic chemotherapy or experimental drugs within 4 weeks before the start of neoantigen treatment, excluding EGFR-TKI and anti-angiogenesis targeted drugs. Patients participated in other anticancer drug clinical trials within 4 weeks. Liver and kidney dysfunction, severe heart disease, coagulation dysfunction, and impaired hematopoietic function. Systemic infection. Any uncertainties that have an impact on the safety or compliance of the patient. Any disease, treatment, abnormal laboratory history or medical history that affects the participant's participation in the entire research process, or the investigator believes that it is not suitable to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients enrolled without disease progression were given neoantigen vaccine combined with EGFR-TKI therapy； Patients with disease progression were given neoantigen vaccine combined with anti-angiogenesis drug therapy. Patients received subcutaneous injection of individualized neoantigen vaccines at a dose of 200ug per peptide once a week for 5 weeks. The targeted drugs are used continuously according to the instructions and dosage until disease progression or intolerance.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: neoantigen vaccine + EGFR-TKI<br> | Drug: neoantigen vaccine + EGFR-TKI<br>* Patients received subcutaneous injection of individualized neoantigen peptides vaccine at a dose of 200ug per peptide once a week for 5 weeks. The targeted drugs are used continuously according to the instructions and dosage until disease progression or intolerance.<br>|
| Experimental: neoantigen vaccine + anti-angioge<br> | Drug: neoantigen vaccine + anti-angioge<br>* neoantigen vaccine + anti-angioge<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. | Safety | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 | Up to 2 years | 
| Overall survival (OS) | OS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 | Up to 2 years | 
| Disease Control Rate(DCR) | DCR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, Individualized neoantigen peptides vaccine, Targeted Drugs, clinical trial, phase I