TCR-T Cell Therapy on Advanced Solid Tumors

Early Phase 1

Recruiting

• Conditions: Pancreatic Cancer
• Interventions: Biological: TCR-T therapy

• Registration Number: NCT05438667
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

The primary aim of this study is to evaluate the efficacy of KRAS mutant antigen specific TCR-T cells in the treatment of patients with advanced solid tumors.

The secondary aim is to evaluate the pharmacokinetic/pharmacodynamic characteristics of TCR-T cell therapy in patients with advanced solid tumors and the survival of TCR-T cells.

The investigators will evaluate the changes of tumor microenvironment after treatment of advanced solid tumors with KRAS mutant antigen specific TCR-T cells; Evaluating the correlation between cytokines and the occurrence of CRS and neurotoxicity

Detailed Description

1.This study is a prospective and single arm clinical study. In this trial, 18 patients with advanced solid tumors with KRAS G12V or G12D mutations and matching HLA-A subtypes are recruited for autologous Tumor-T Cell Receptor (TCR) -Mediated T Cells therapy(TCR-T) therapy.Within 3 - 5 days after pretreatment, subjects will receive a single TCR-T infusion with an infusion dose of about 1 × 10⁹～1 × 10¹⁰. Once every 12 hours within 24 hours after TCR-T cell infusion, recombinant human interleukin-2 will be injected intravenously for 5 days .

After 3 months of treatment, the patient's condition was evaluated. If the subject did not occur tumor progression and did not occur adverse events (AEs) of level 3 or higher, a second TCR-T cell reinfusion can be performed based on researcher's judgment (informed consent form needs to be signed again).

The study will evaluate the safety of TCR-T treatment by observing adverse events after cell therapy; evaluate the effectiveness of TCR-T compared to the results or historical data of the subject's own previous standard treatment regimen;and collect blood before and after cell infusion, measure the number and activity of TCR-T cells, and evaluate the pharmacokinetic (PK) characteristics of TCR-T.

Study Timeline

• Study First Submitted: 2022-06-07
• Study First Submitted QC: 2022-06-24
• Study First Posted: 2022-06-30
• Study Start: 2023-06-01
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-01
• Last Update Posted: 2025-09-08
• Primary Completion: 2028-06-30
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

1. Intracranial metastasis or Patients with moderate or severe hydrothorax need drain placement to relieve symptoms.
2. Active pulmonary tuberculosis
3. Human immunodeficiency virus (HIV) positive；
4. Active Hepatitis B or Hepatitis C infection；
5. Pregnant women and lactating females；
6. Previous or concurrent history of other malignant tumors. Exceptions include curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy;
7. Patients with central nervous metastases；
8. Serious, uncontrolled comorbidities that may affect protocol compliance or interfere with interpretation of results，or any serious medical condition that may affect the safety of the subjects ;
9. History of clinically significant respiratory diseases or other respiratory diseases that seriously affect Pulmonary function;
10. Any active autoimmune disease,any condition requiring steroid hormones or immunosuppressive therapy( including but not limited to systemic lupus erythematosus, sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc., require > 10 mg/D of prednisone or equivalent hormone）
11. A history of organ transplantation；
12. A history of myocardial infarction and severe arrhythmia within six months；Ineligible also includes uncontrolled hypertension, coronary heart disease, stroke, liver cirrhosis, nephritis and other serious complications;
13. Those who have a history of psychotropic drug abuse and cannot quit or have a history of psychiatric impairment；
14. Participants with an allergic constitution, known sensitivity to human serum albumin, cyclophosphamide, fludarabine and interleukin 2;
15. Those with bleeding or thromboembolic tendency：bleeding symptoms of clinical significance or a clear tendency to bleeding within 2 weeks prior to entering the study. And those with hereditary or acquired bleeding and thrombotic tendencies； serious arterial/venous thromboembolic events occurred in the previous 6 months;
16. Other severe, acute or chronic medical or mental illnesses that in the investigator's judgement will might be increase the risk associated with the patient's participation in the study or interfere with interpretation of research results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TCR-T treatment group	TCR-T therapy	Within 3-5 days after pretreatment, subjects will receive a single TCR-T infusion with an infusion dose of about 1 × 10⁹～1 × 10¹⁰.Once every 12 hours within 24 hours after TCR-T cell infusion, recombinant human interleukin-2 will be injected intravenously for 5 days. After 3 months of treatment, the patient's condition was evaluated. If the subject did not occur tumor progression and did not occur adverse events (AEs) of level 3 or higher, a second TCR-T cell reinfusion can be performed .

Primary Outcome Measures

Name	Time	Method
objective response rate（ORR）	At 12months after the TCR-T cell infusion	The objective response rate is calculated based on the patient population with measurable lesions at baseline, with efficacy determined by comparing tumor burden before and after treatment. According to RECIST 1.1 criteria，Complete Response (CR): Disappearance of all target lesions with no new lesions. Partial Response (PR): ≥30% reduction in the sum of diameters of target lesions. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions or appearance of new lesions. Stable Disease (SD): Changes not meeting any of the above thresholds.

Secondary Outcome Measures

Name	Time	Method
Peak plasma concentration (Cmax)	1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion	Peak plasma concentration (Cmax) refers to the maximum concentration of TCR-T cells in peripheral blood after the TCR-T cells infusion.
Peak value of cytokines	1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion	The peak value of cytokines within 1 month after TCR-T cell infusion .
Event free survival period	At 12months after the TCR-T cell infusion	The event free survival period (until the time of treatment failure) refers to the time from entering the trial to any treatment failure, including disease progression or cessation of treatment for any reason (such as disease progression, toxic reactions, subject willingness, initiation of new treatment without clear progression, or death).According to RECIST version 1.1, the tumor evaluation of all subjects will be evaluated within 12 months after TCR-T treatment.
The disease-free survival period	At 12months after the TCR-T cell infusion	The disease-free survival period refers to the time from obtaining disease-free status or reaching complete response until recurrence or death due to acute toxicity of tumors or treatment.
Area under the plasma concentration versus time curve (AUC)	1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion	Area under the plasma concentration versus time curve (AUC) is used to access the absorbed TCR-T cells dose into human blood circulation after TCR-T cells injection.
Peak time (Tmax)	1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion	Peak time (Tmax) refers to the time when the blood concentration reaches the peak after TCR-T cells injection.
Progression free survival (PFS)	At 12months after the TCR-T cell infusion	Progression free survival refers to the time from TCR-T infusion to the first occurrence of disease or death from any cause.According to RECIST version 1.1, the tumor evaluation of all subjects will be evaluated within 12 months after TCR-T treatment.
Cell number of TCR-T cells in peripheral blood	1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion	Cell numbers of TCR-T cells after the injection of TCR-T cells
Adverse events	12months after TCR-T infusion	The type, incidence and severity of adverse events include abnormal laboratory examination results with clinical significance after treatment, abnormal physical examination and blood examination results, bone marrow examination results, etc. Clinical and laboratory adverse events will be classified according to the National Cancer Institute general terminology standard for adverse events (NCI CTCAE) version 5.0.
duration of response(DOR)	12months after TCR-T infusion	DOR is defined as the time from the first confirmed objective response to disease progression or recurrence.
The overall survival(OS)	At 12months after the TCR-T cell infusion	The overall survival period refers to the time of the TCR-T infusion to the death of the patient for any cause.
Time to progression (TTP)	12months after the TCR-T cell infusion	Time to progression (TTP) refers to the time from TCR-T infusion to objective tumor progression.According to RECIST version 1.1, the tumor evaluation of all subjects will be evaluated within 12 months after TCR-T treatment.
The duration of efficacy	At 12months after the TCR-T cell infusion	The duration of efficacy refers to the time from reaching the treatment effectiveness (i.e. CR or PR) standard until the first definite recurrence or progression is achieved.

Trial Locations

Locations (1)

Sun Yat-sen Memorial Hospital; 🇨🇳 Guangzhou, Guangdong, China