Clinical trial NCT06432075: Neoantigen Reactive T Cells c for Chinese Patients With Advanced Gastric Cancer
Official title: Single Arm Clinical Prospective Study of Neoantigen Reactive T Cells (NRTs) in the Treatment of Chinese Patients With Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Advanced Gastric Cancer
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2024-05-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see the safety and efficient of neoantigen reactive T cells (NRTs) in the treatment of Chinese patients with advanced gastric cancer.

Detailed description: The tumor-specific "none-self" immunogenic neoantigens encoded by either viral genes or somatic mutation genes, possess the potential to induce specific anti-cancer immunity, including cellular and humoral immune responses. Today, numerous clinical trials demonstrate that although these "none-self" antigens initiate the antigen-specific immunoglobulin G antibodies and cluster of differentiation 4（CD4）+/cluster of differentiation 8（CD8）+T-cells response, not all of them show a clinical benefit in the response rate, progression-free survival or overall survival.Personalized cell therapy maybe own a breakthrough in the treatment of those gastric cancer patients without standard options.The investigators' center has successfully established a new method for preparing personalized neoantigen reactive T cells(NRTS) for adoptive cell therapy(ACT). Today, the investigators will carry out a single arm clinical prospective study of NRTs for the treatment of Chinese patients with advanced gastric cancer. Participants are assigned to receive 4 circles of cell therapy, and IL-2 continuous intravenous infusion（CIV） will also be given for 5 consecutive days after each time's cell infusion. The safety and clinical response rate（RR） are evaluated. Biomarkers and immunological markers are also monitored.

Eligibility criteria: Inclusion Criteria:

1. Voluntarily join the study and sign the informed consent;
2. Age: 18-75 years old, male or female;
3. Subjects with advanced gastric cancer who had received systematic standard treatment before enrollment and had no effective treatment at present. (Note: The effective treatment means refer to the latest version of the "Gastric Cancer Diagnosis and Treatment Guide" issued by China's "Chinese Clinical Oncology Society".) ;
4. Have at least one measurable lesion according to imRECIST evaluation criteria;
5. Expected survival ≥5 months (starting from the collection of tissue samples for sequencing);
6. The Eastern Cancer Consortium (ECOG) score was 0 or 1 or 2;
7. The following hematological indicators should be met: neutrophil count ≥ 1.5×109/L; Hemoglobin ≥ 10.0 g/dL; Platelet count ≥ 50×109/L;
8. The following biochemical indicators should be met: total bilirubin ≤2.0× upper limit of normal value (ULN); AST and ALT ≤2.0×ULN; Serum creatinine ≤1.5×ULN.
9. Before lymphocyte clearance preadministration: 1) any chemotherapy, small molecule targeted drugs and other antitumor therapy received have passed the 3-week washout period, and the toxic side effects have returned to grade 1 or lower (excluding hair loss, vitiligo and other events as determined by the investigator to be tolerated); 2) If surgical treatment is performed within 3 weeks, toxicity has returned to grade 1 or lower; 3) The immunotoxicity of major organs has returned to grade 1 or lower after receiving any antibody drug treatment, and the washout period of PD-1 antibodies has reached 6 weeks, and CTLA-4 antibodies and other antibodies have passed the washout period of 4 weeks.

Exclusion Criteria:

1. Subjects infected with HBV, HCV, HIV, syphilis and tuberculosis;
2. Uncontrolled coronary artery disease or asthma, uncontrolled cerebrovascular disease or what the investigator considers Other diseases not included in the group;
3. Patients with a history of bone marrow or organ transplantation; Patients with coagulation dysfunction;
4. Patients with immune deficiency diseases or autoimmune diseases who are treated with immunosuppressive drugs;
5. Central nervous system (CNS) metastatic and/or cancerous meningitis;
6. People who may be allergic to immunotherapy;
7. Drug abuse, clinical or psychological or social factors that affect informed consent or the conduct of the study;
8. Pregnant and lactating women;
9. Participating in other clinical trials;
10. An uncertainty that the investigator believes has an impact on the subject's safety or compliance.

Primary outcomes:
measure: Number of participants with Adverse Events
timeFrame: up to 6 months
Secondary outcomes:
measure: Response Rate
timeFrame: Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months
measure: Progression free survival (PFS)
timeFrame: Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months
Other outcomes:
measure: Overall Survival (OS)
timeFrame: Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months
measure: Interferon-gama change of PBMC cells in the peripheral blood stimulated by tumor antigens
timeFrame: Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months
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