Using Neoantigen Peptide Vaccine/Neoantigen-based DC to Treat Advanced Malignant Solid Tumors

Study Overview
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Brief Summary
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In this study, the investigators provide a personalized tumor neoantigen peptide vaccine/neoantigen-based DC treatment to patients with advanced malignant solid tumors. The investigators observe the post-treatment tumor burden status, the immune response induced by immune preparations, and the prolongation of patient survival time, aiming to evaluate the effectiveness and safety of the neoantigen-based DC treatment.

Detailed Description
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This study is conducted in accordance with the Declaration of Helsinki and the guidelines of the Consolidated Standards of Reporting Trials. 20 patients with primary or metastatic melanoma, gastrointestinal tumor, breast cancer, cervical cancer, pancreatic cancer, lung cancer, or other malignant tumors will be recruited in this study. With doctor's assessment, a personalized tumor neoantigen peptide vaccine or neoantigen-based DC treatment plan will be designed for each participant： Collecting venous blood samples; Blood PBMC exome sequencing; RNA transcriptome sequencing; Classifying HLA alleles; Performing bioinformatics analysis, finding meaningful mutations and about 10 neoantigen sequences for each patient; Synthesizing peptide neoantigens; Preparation of the personalized tumor neoantigen peptide vaccine or generating the personalized tumor neoantigen DC therapeutic immune preparation. Participants will receive 5-6 subcutaneous injections of the vaccine or DC preparation within a treatment period of 14 weeks. After treatment, participants will have 3 follow-up visits during 9-months. Venous blood collection, physical examination, ECOG Performance Status Scale assessment, CT/MRI scan, X-ray examination, laboratory examination, and other necessary examinations are required at each follow-up visit.

Official Title
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A Clinical Study of Personalized Tumor Neoantigen Peptide Vaccine/Neoantigen-based Dendritic Cells in the Treatment of Advanced Malignant Solid Tumors

Conditions
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Advanced Malignant Solid Tumors

Intervention / Treatment
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* Drug: Neoantigen peptide vaccine
* Drug: Neoantigen-based DC immune preparation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With inoperable advanced malignant solid tumors, including melanoma, gastrointestinal tumor, breast cancer, pancreatic cancer, cervical cancer, lung cancer, etc. Failed in standard treatment or voluntarily give up other treatment, and been longer than 2 weeks from the end of the last anti-tumor treatment Had disease progression prior to treatment Expected survival ≥ 3 months ECOG performance status of 0, 1, or 2 With a negative pregnancy test for females of childbearing age Able to take effective contraceptive measures and ensure that there is no birth plan within half a year of the study Not positive for HIV, HBV, HCV, or TP ALT/AST ≤ 2.5 times the upper limit of normal ALP ≤ 2.5 times the upper limit of normal Serum creatinine ≤1.6 mg/dL Total bilirubin ≤ 1.5 mg/dL In the absence of granulocyte colony-stimulating factor support, proportion of lymphocytes > 20%, absolute neutrophil count ≥ 1x10^9/L, white blood cell count ≥ 3x10^9/L, platelet count ≥ 100×10^9/L, hemoglobin > 8.0 g/dL, CD4+ cell count > 200/μL With normal coagulation test and ECG Able to understand and willing to sign a written informed consent form Exclusion Criteria: Pregnant or breastfeeding women Patients with brain metastases Had immunosuppressant therapy within 1 month or received other immunotherapy within 3 months Participated in other clinical study within 30 days With severe allergies or histories of severe allergy With splenectomy With primary or secondary immunodeficiency diseases or autoimmune diseases (including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, psoriasis, uncontrolled asthma, etc.) Had oral, intramuscular, or intravenous corticosteroids within 1 month. However, inhaled corticosteroids are allowed to treat respiratory insufficiency (such as chronic obstructive pulmonary disease), as well as topical steroids With uncontrollable epilepsy, central nervous system disorder, or neurological disease with loss of cognitive ability With a history of chronic alcohol or drug abuse within 6 months With unstable systemic diseases (including active infection, liver cirrhosis, chronic renal failure, severe chronic pulmonary disease, unstable hypertension, unstable angina, congestive heart failure, myocardial infarction within 1 year, etc.) With a history of other malignant tumors in the past 5 years (excluding those who have been clinically cured, and squamous cell carcinoma or skin basal cell carcinoma) Those the researcher believed inappropriate to participate in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoantigen peptide vaccine/neoantigen-based DC treatment<br>Patients assigned to the neoantigen peptide vaccine/neoantigen-based DC treatment group will receive 5-6 subcutaneous injections of neoantigen peptide vaccine or neoantigen-based DC immune preparation within a 14-week treatment period. | Drug: Neoantigen peptide vaccine<br>* Personalized tumor neoantigen peptide vaccine<br>Drug: Neoantigen-based DC immune preparation<br>* Personalized tumor neoantigen DC therapeutic immune preparation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival (PFS) is the time from the inoculation of the individualized neoantigen immune preparation to disease progression or death from various causes for all patients. Tumor assessment is performed according to the RECIST1.1 standard. The analysis of this indicator includes results of tumor assessments performed during the treatment period and the follow-up period. If a patient has several indicators that can be judged as disease progression (PD), the indicator that appears first will be used for PFS analysis. Relapse, new tumors, or death are considered to have reached the end of the study. For patients who had not experienced disease progression at the end of the study, the last time the patient had no disease progression was used as censoring data. | 9 months after treatment | 
| Overall response rate | Overall response rate is the proportion of patients whose tumor shrinkage reaches a certain amount and remains for a certain period of time, including complete response (CR) and partial response (PR) cases. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) was used to evaluate the objective response of tumors. Subjects must have measurable tumor lesions at baseline, and the efficacy evaluation is divided into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). | 1 week after treatment | 
| Tumor makers | CEA，CA19-9，CA125 | 9 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is the time from inoculation of the individualized neoantigen immune preparation to death due to various causes for all patients. | 9 months after treatment | 
| Disease control rate | Disease control rate is the percentage of patients who have a complete response (CR), partial response (PR), and stable disease (SD) to the treatment. | 1 week after treatment | 
| Tumor imaging | CT/MRI scan, X-ray examination etc. | 9 months after treatment | 
| Peripheral blood cytokines | Changes in peripheral blood cytokines after treatment, including IFN-γ, TNF, IL-2, etc. | 9 months after treatment | 
| ECOG | Eastern Cooperative Oncology Group (ECOG) Performance Status Scale. This scale describes patients' level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). Researchers worldwide consider the ECOG Performance Status Scale when planning cancer clinical trials to study new treatments. There are 6 grades in ECOG, the minimum value is 0 and the maximum value is 5, while a higher score indicates a worse condition. | 9 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoantigen Peptide Vaccine, Neoantigen-based Dendritic Cells, Therapeutic immune preparation, Advanced Malignant Solid Tumors, Progression-free Survival, Overall Survival, Overall Response Rate