Clinical trial NCT05749627: Using Neoantigen Peptide Vaccine/neoantigen-based DC to Treat Advanced Malignant Solid Tumors
Official title: A Clinical Study of Personalized Tumor Neoantigen Peptide Vaccine/neoantigen-based Dendritic Cells in the Treatment of Advanced Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Advanced Malignant Solid Tumors
Keywords: Neoantigen Peptide Vaccine
Neoantigen-based Dendritic Cells
Therapeutic immune preparation
Advanced Malignant Solid Tumors
Progression-free Survival
Overall Survival
Overall Response Rate
Lead sponsor: The First Affiliated Hospital of Nanchang University
Sponsor class: OTHER
Collaborators: name: Shanghai Dengding BioAI Co.
First posted: 2023-03-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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：

1. Collecting venous blood samples;
2. Blood PBMC exome sequencing;
3. RNA transcriptome sequencing;
4. Classifying HLA alleles;
5. Performing bioinformatics analysis, finding meaningful mutations and about 10 neoantigen sequences for each patient;
6. Synthesizing peptide neoantigens;
7. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival
timeFrame: 9 months after treatment
measure: Overall response rate
timeFrame: 1 week after treatment
measure: Tumor makers
timeFrame: 9 months after treatment
Secondary outcomes:
measure: Overall survival
timeFrame: 9 months after treatment
measure: Disease control rate
timeFrame: 1 week after treatment
measure: Tumor imaging
timeFrame: 9 months after treatment
measure: Peripheral blood cytokines
timeFrame: 9 months after treatment
measure: ECOG
timeFrame: 9 months after treatment
Other outcomes:
Locations:
city: Nanchang
country: China
facility: First Affiliated Hospital of Nanchang University
state: Jiangxi
Study officials:
References: