TCR-T Cell Therapy on Advanced Pancreatic Cancer
- Conditions
- Pancreatic Cancer
- Interventions
- Biological: TCR-T therapy
- Registration Number
- NCT05438667
- 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 pancreatic cancer.
The secondary aim is to evaluate the pharmacokinetic/pharmacodynamic characteristics of TCR-T cell therapy in patients with advanced pancreatic cancer and the survival of TCR-T cells.
The investigators will evaluate the changes of tumor microenvironment after treatment of advanced pancreatic cancer 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 pancreatic cancer with KRAS G12V or G12D mutations and matching HLA-A\*11:01 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 14 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 (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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 18
Not provided
- Intracranial metastasis or Patients with moderate or severe hydrothorax need drain placement to relieve symptoms.
- Active pulmonary tuberculosis
- Human immunodeficiency virus (HIV) positive；
- Active Hepatitis B or Hepatitis C infection；
- Pregnant women and lactating females；
- 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;
- Patients with central nervous metastases；
- 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 ;
- History of clinically significant respiratory diseases or other respiratory diseases that seriously affect Pulmonary function;
- 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）
- A history of organ transplantation；
- 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;
- Those who have a history of psychotropic drug abuse and cannot quit or have a history of psychiatric impairment；
- Participants with an allergic constitution, known sensitivity to human serum albumin, cyclophosphamide, fludarabine and interleukin 2;
- 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;
- 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 14 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 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.
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.
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.
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 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.
- Secondary Outcome Measures
Name Time Method Peak time (Tmax) 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.
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.
Peak plasma concentration (Cmax) 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.
Area under the plasma concentration versus time curve (AUC) 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.
Cell number of TCR-T cells in peripheral blood 12months after the TCR-T cell infusion Cell numbers of TCR-T cells after the injection of TCR-T cells
Peak value of cytokines 1 month after TCR-T cell infusion The peak value of cytokines within 1 month after TCR-T cell infusion .
Trial Locations
- Locations (1)
Sun Yat-sen Memorial Hospital
🇨🇳Guangzhou, Guangdong, China