## Protocol Section
### Identification Module
**NCT ID:** NCT06432075

**Brief Title:** 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

#### Organization Study ID Info
**ID:** Neoantigen T Cells
#### Organization
**Class:** OTHER
**Full Name:** First Affiliated Hospital of Wenzhou Medical University
### Status Module
#### Completion Date
**Date:** 2026-12-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-01-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** First Affiliated Hospital of Wenzhou Medical University

#### Responsible Party

**Investigator Affiliation:** First Affiliated Hospital of Wenzhou Medical University

**Investigator Full Name:** Shen Xian

**Investigator Title:** Chief Physician

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Advanced Gastric Cancer

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- EARLY_PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Biological: Neoantigen Reactive T Cells(NRTs)

**Label:** Neoantigen Reactive T Cells

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Neoantigen Reactive T Cells

**Description:** 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.

**Name:** Neoantigen Reactive T Cells(NRTs)

**Type:** BIOLOGICAL

### Outcomes Module

#### Other Outcomes

**Description:** the duration is measured from the time of treatment to the time of death

**Measure:** Overall Survival (OS)

**Time Frame:** 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

**Description:** T cells in the peripheral blood stimulated by tumor antigens for 24 hr，and then Interferon-gama secretion is measured

**Measure:** Interferon-gama change of PBMC cells in the peripheral blood stimulated by tumor antigens

**Time Frame:** 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

#### Primary Outcomes

**Description:** using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients

**Measure:** Number of participants with Adverse Events

**Time Frame:** up to 6 months

#### Secondary Outcomes

**Description:** Response Rate（RR）will be evaluated according Response Evaluation Criteria in Solid Tumors

**Measure:** Response Rate

**Time Frame:** 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

**Description:** the duration of progression free survival is measured from the time of treatment to the first date that recurrent or progressive disease or for any reason of death is objectively documented.

**Measure:** Progression free survival (PFS)

**Time Frame:** 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

### Eligibility Module

**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.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** 13968888872@163.com

**Name:** Xian Shen

**Phone:** 13968888872

**Role:** CONTACT

### IPD Sharing Statement Module

**Description:** Publications

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000013272

- Term: Stomach Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16064

- Name: Stomach Neoplasms

- Relevance: HIGH

- As Found: Gastric Cancer

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16062

- Name: Stomach Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T5486

- Name: Stomach Cancer

- Relevance: HIGH

- As Found: Gastric Cancer

### Condition Browse Module - Meshes

- ID: D000013274

- Term: Stomach Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Analg

- Name: Analgesics

### Intervention Browse Module - Browse Leaves

- ID: M19537

- Name: Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M6727

- Name: Cyclophosphamide

- Relevance: LOW

- As Found: Unknown

- ID: M231

- Name: Albumin-Bound Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M10411

- Name: Interleukin-2

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
