TCRx_T Cells for Advanced or Recurrent Gastric/Gastroesophageal Junction Cancer After Failure of First Chemotherapy

Exploratory Clinical Study of TCRx_T Cells in the Treatment of Advanced or Recurrent Gastric/Gastroesophageal Junction Cancer After Failure of First Chemotherapy

To observe and determine the safety, tolerability, cellular pharmacokinetics and efficacy of TCRx T cells in patients with advanced or recurrent gastric/gastroesophageal junction cancer after failure of first chemotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer; Gastroesophageal-junction Cancer
• Intervention / Treatment: Biological: Tcrx T cell

Detailed Description

1. Sign the informed consent for clinical trials
2. Subject screening
3. Extract the blood of the subjects and isolate the PBMC
4. Find a patient-specific tumor-specific TCR sequence combination, which is a multi-targeted tumor-specific combination.
5. Transfer of personalized tumor-specific TCRs into patient autologous CD8 T cells by gene editing
6. Large-scale culture and expansion of gene-edited T cells
7. T cell viability, infection efficiency and microbial detection in hospital
8. Calculate the number of cells in the patient's body according to TCRx T
9. Injecting TCRx T cells back into the subject
10. Within 7 days after the injection, the subject's post-dose reaction should be closely observed in the hospital
11. After the first injection, continue to reinfuse TCRx T cells up to 4 times according to the treatment effect and the incidence of adverse events, and be hospitalized after each injection to closely monitor possible adverse events

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 years old;
2. Histologically confirmed advanced/locally advanced or metastatic gastric cancer at the stomach or gastroesophageal junction, progressed after first-line chemotherapy, or recurrence after gastric/gastroesophageal junction surgery combined with neoadjuvant/adjuvant chemotherapy
3. Expected survival time ≥ 3 months
4. Eastern Cooperative Oncology Group (ECOG) score 0-2
5. According to the Response Evaluation Criteria for Solid Tumors (RECIST 1.1), at least one one-dimensional, measurable tumor (short-axis diameter greater than 1 cm)
6. Normal bone marrow hematopoietic function: (leukocytes≥4000 cells/㎕, neutrophils≥1500 cells/㎕, platelet counts≥100000 cells/㎕)
7. Normal liver and kidney function: serum bilirubin <1.5mg/dl, AST (SGOT) and ALT (SGPT) <2.5UNL, alkaline phosphatase <5UNL; serum creatinine <1.5mg/dl;
8. Men and women must take appropriate contraceptive measures.

Exclusion Criteria:

1. Patients with previous non-gastric/gastroesophageal junction malignant tumor
2. History of severe acute allergy
3. There is an uncontrolled infection
4. History or clinical evidence of central nervous system (CNS) metastasis or leptomeningeal carcinomatosis
5. History of cerebrovascular accident within the past 6 months, including transient ischemic attack (TIA), pulmonary embolism or untreated deep vein thrombosis (DVT)
6. History of one or more of the following cardiovascular diseases within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass grafting, symptomatic peripheral vascular disease , NYHA type III or IV congestive heart failure
7. Poor control of hypertension
8. QT interval >480ms
9. Evidence of active bleeding or bleeding tendency
10. Clinically significant gastrointestinal abnormalities, such as bleeding, obstruction, and high risk of perforation
11. Grade 3 or 4 diarrhea
12. Any serious and/or unstable previous medical, psychiatric, or other circumstances that may affect subject safety, provide informed consent, or comply with research procedures
13. Unable or unwilling to stop using illicit drugs for at least 14 days or drug half-life (whichever is longer) before and during the first study drug administration
14. Treated with any of the following anticancer therapies: radiotherapy, tumor embolization or chemotherapy, immunotherapy, biological therapy within 14 days before the first dose; neoadjuvant chemotherapy or adjuvant chemotherapy must be at least 6 months before the start of the study Finish
15. Any persistent toxicity greater than grade 1 and/or worsening in severity from prior anticancer therapy, except for alopecia
16. Participate in a clinical trial of another investigational drug within 30 days prior to the start of the study
17. Pregnant or lactating women
18. Men or women planning to become pregnant within the next six months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TCRX-T; ① 1x10^7/m2 ; 3x10^7/m2；1x10^8/m2；3x10^8/m2；1x10^9/m2。	Biological: Tcrx T cell; Sequential IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor volume	RECIST 1.1	about 2 years
Overall Survival	The time from randomization to death due to any reason.	about 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs	CTCAE5.0	about 2 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: TCRx Therapeutics Co.Ltd

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): March 1, 2028

Study Registration Dates

• First Submitted: July 3, 2022
• First Submitted That Met QC Criteria: July 3, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Gastric Cancer; T Cell Receptor; Gastroesophageal-junction Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: KSH02-TCRXT-CJ

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No