Neoantigen Reactive T Cells c for Chinese Patients With Advanced Gastric Cancer

NCT ID: NCT06432075

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2026-12-01

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.

Conditions

Advanced Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoantigen Reactive T Cells

Peripheral blood lymphocytes will be collected and neoantigen reactive T cells(NRTs) will be generated in the laboratory;nab-paclitaxel 100-200mg/m2/D will be i.v. for 7 days before cell infusion; Cyclophosphamide 300mg/m2/D will be i.v. for 2 and 3 days before cell infusion; NRTs 0.5\~1 x 10\^10, will be i.v.Q3 weeks for total 4 doses;Interleukin-2 (IL-2) will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 1000,000 international unit per day.All Patients will receive a total of 4 cycles of treatment.

Group Type: EXPERIMENTAL

Neoantigen Reactive T Cells(NRTs)

Intervention Type: BIOLOGICAL

Neoantigen Reactive T Cells in an expected volume of 100 milliliter（mL） will be given by intravenous injection over 2-10 minutes through either a peripheral or a central line.

Interventions

Neoantigen Reactive T Cells(NRTs)

Neoantigen Reactive T Cells in an expected volume of 100 milliliter（mL） will be given by intravenous injection over 2-10 minutes through either a peripheral or a central line.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Shen Xian

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Xian Shen

Role: CONTACT

13968888872@163.com

13968888872

Other Identifiers

Neoantigen T Cells

Identifier Type: -

Identifier Source: org_study_id