NCT05580796招募中早期 1 期
Investigator Initiated Clinical Trial on the Tolerance, Safety and Preliminary Efficacy of KSH01-TCRT Injection in Solid Tumor Subjects
TCRx Therapeutics Co.Ltd1 个研究点 分布在 1 个国家目标入组 50 人开始时间: 2022年10月11日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Number of participants in treatment related adverse events assessed by CTCAE v4.0
研究概览
简要总结
- . safety and tolerance
- . objective response rate
详细描述
- . To evaluate the safety and tolerance of autologous TCR-T cells in target positive solid tumor patients.
- . Preliminary evaluation of objective response rate (ORR) of autologous TCR-T cells in target positive solid tumor patients (such as esophageal cancer, gastric cancer, head and neck cancer, bladder cancer, melanoma, sarcoma, etc.)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation in clinical research; Fully understand the study and voluntarily sign the informed consent form; Willing to follow and able to complete all test procedures;
- •Male or female, 18 to 70 years old (including boundary value);
- •Malignant solid tumors failed to receive standard treatment;
- •HLA-A * 02 is positive and tumor target is positive (the staining intensity of target tumor cells is divided into 0, 1+, 2+, 3+, and more than 30% of cancer cells express 2+or 3+positive as the target is positive)
- •. All toxic reactions caused by previous anti-tumor treatment are alleviated to grade 0-1 (according to NCI CTCAE version 5.0) or to an acceptable level of inclusion/exclusion criteria. Other poisons such as alopecia and vitiligo that researchers believe do not pose a safety risk to subjects
- •There is sufficient organ function (no medical support such as blood transfusion and granulocyte colony stimulating factor within 14 days before cell transfusion), which is defined as follows:
- •6.1) Blood system:
- •6.1.1) Neutrophil count (ANC) is not lower than the lower limit of normal value of the center;
- •6.1.2) White blood cell (WBC) shall not be lower than the lower limit of normal value of the center;
- •6.1.3) Platelet count (PLT) shall not be lower than the lower limit of normal value of the center;
- •6.1.4) Hemoglobin (Hb) shall not be lower than 0.8 * LLN (lower limit of normal value);
- •6.2) Liver function:
- •6.2.1) Total bilirubin (TBIL) ≤ 2.0 × Upper limit of normal (ULN), Gilbert disease subjects should be ≤ 3 × ULN；
- •6.2.2) AST, ALT ≤ 3 × ULN (in the dose expansion stage, the subjects with liver metastasis or liver cancer can be ≤ 5 × ULN）； Alkaline phosphatase (ALP) ≤ 2.5 × ULN (bone metastasis subject, ALP ≤ 5 × ULN）；
- •6.3) Renal function:
- •6.3.1) Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 ml/min (Cockcroft Gault formula: ([140 age] × Weight [kg] × [0.85 for women only])/(72 × Creatinine (mg/dl));
- •6.3.2) Qualitative urine protein ≤ 1+; If the urine protein is qualitative ≥ 2+, a 24-hour urine protein quantitative test is required. If the 24-hour urine protein quantitative test is less than 1 g, it is acceptable;
- •6.4) Coagulation function: those not receiving anticoagulation treatment: International normalized ratio (INR), activated partial thromboplastin time (APTT) should be ≤ 1.5 × ULN； Subjects with liver metastasis or liver cancer should be ≤ 2 × ULN；
- •Physical condition: The score of the Eastern American Cooperative Oncology Group (ECOG) was 0-1;
- •Expected survival time ≥ 12 weeks;
- •According to RECIST 1.1, there is at least one measurable lesion (dose expansion stage) or evaluable lesion (dose increase stage);
- •After evaluation, enough PBMC cells can be collected from the subjects to prepare autologous TCR-T cells;
- •After evaluation, the prepared autologous TCR-T cells are sufficient in quantity and qualified in quality, and can be used for clinical reinfusion of corresponding dose;
- •The blood pregnancy result of female subjects with fertility within 3 days before cell transfusion was negative, and they were willing to sign informed consent from the end of the last medication to 6 months, keep abstinence or take medically approved effective contraceptive measures (such as intrauterine device, pregnancy avoidance device);
- •Male subjects are willing to keep abstinence or take medically approved effective contraceptive measures within 6 months from signing the informed consent form to the end of the last medication, and do not donate sperm during this period;
- •All subjects should provide tumor tissue samples that can be used for target analysis, which should be archived samples or fresh biopsy samples (bone biopsy samples are not accepted). Only those with positive target expression can enter the study.
排除标准
- •History of serious allergic diseases, allergic history of serious drugs (including non marketed test drugs) or known allergy to any component of the proposed drugs (including pre-treatment drugs) in this protocol;
- •Previous coronary artery reconstruction;
- •Evidence of major haemorrhagic disorder or other obvious bleeding risks:
- •3.1) Previous history of intracranial hemorrhage or intracerebral hemorrhage;
- •3.2) The tumor focus invades large vessels and has obvious risk of bleeding;
- •3.3) Thrombosis or embolism occurred within 6 months before cell transfusion;
- •3.4) Clinically significant hemoptysis or tumor hemorrhage occurred within 1 month before cell transfusion;
- •3.5) Anticoagulant therapy (except low molecular weight heparin) for therapeutic purposes was used within 2 weeks before cell transfusion;
- •3.6) Within 10 days before cell reinfusion, they have used antiplatelet drugs, such as aspirin (>325 mg/day), clopidogrel (>75 mg/day), dipyridamole, ticlopidine or cilostazol;
- •Have received the following treatments or drugs before cell reinfusion:
- •4.1) Unhealed wound, ulcer or fracture within 28 days before cell reinfusion;
- •4.2) Inoculate live attenuated vaccine within 28 days before cell reinfusion;
- •4.3) The cells were treated with nitrosourea or mitomycin C within 6 weeks before reinfusion; Oral fluorouracil therapy was received 2 weeks before cell reinfusion or within 5 half lives of the drug (whichever is longer);
- •4.4) Within 2 weeks before cell reinfusion, the patient has received corticosteroids, or it is estimated that corticosteroids may be required during blood collection, cell collection or cell reinfusion; Except for the following cases: short-term (≤ 7 days) prednisone with a dose not higher than 10 mg/d or equivalent dose is used to prevent or treat non autoimmune conditions; Corticosteroids for local, nasal, intraocular, articular cavity or inhalation;
- •It is known that there is leptomeningeal metastasis, or uncontrolled or symptomatic central nervous system metastasis, with clinical symptoms, brain edema, spinal cord compression and/or progressive growth. Subjects with a history of central nervous system metastasis or spinal cord compression can be accepted if they have definitely received treatment and stopped using anticonvulsants and steroids 8 weeks before cell reinfusion, and their clinical manifestations are determined to be stable by the investigator;
- •Presence of any form of primary immunodeficiency;
- •Presence of any active autoimmune disease, Or asthmatic subjects who have a history of autoimmune diseases and are expected to relapse (including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, and asthma requiring medical intervention with bronchodilators. The following cases are excluded: type 1 diabetes; skin diseases that do not require systemic treatment [such as vitiligo, psoriasis, alopecia] ； Hypothyroidism requiring only hormone replacement therapy; Asthma that has been completely relieved in childhood does not need any intervention in adulthood; Or other patients who are expected to have no relapse under the condition of no external trigger);
- •Within 6 months before cell reinfusion, the following conditions occurred: myocardial infarction, severe/unstable angina, arrhythmia with clinical significance and requiring clinical intervention, cerebrovascular accident/stroke, transient ischemic attack, subarachnoid hemorrhage, and cardiac insufficiency with NYHA grade ≥ II;
- •At present, there are uncontrollable pleural, pericardial and peritoneal effusion;
- •Before cell reinfusion, there were:
- •10.1) congenital long QT syndrome
- •10.2) pacemaker use
- •10.3) left ventricular ejection fraction (LVEF)<50%
- •10.4) QTcF interval>480 msec (QTcF=QT/(RR ^ 0.33)
- •10.5) cardiac troponin I or T>2.0 ULN
- •10.6) poorly controlled diabetes mellitus (fasting glucose ≥ 13.3 mM)
- •10.7) poorly controlled hypertension (systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg);
- •10.8) Forced expiratory volume in the first second (FEV1) ≤ 60% or oxygen therapy is required;
- •During screening or before cell reinfusion, fever of unknown cause occurred>38.5 ° C (according to the judgment of the investigator, fever caused by tumor can be included in the group);
- •History of allograft transplantation is known;
- •Known history of alcohol abuse, psychotropic substance abuse or drug abuse;
- •Have a clear history of neurological or mental disorders, such as epilepsy, dementia, schizophrenia, etc;
- •Known to have acquired immunodeficiency syndrome (AIDS);
- •Serious active virus, bacterial infection or uncontrolled systemic fungal infection are known;
- •Virology test results (HIV, CMV, HSV, HPV, EBV, syphilis) are positive;
- •HBsAg positive or HBcAb positive, and HBV-DNA>200 IU/mL; HCV Ab is positive, and HCV RNA is higher than the lower detection limit of the research center;
- •According to the judgment of the investigator, the basic condition of the subject may increase the risk of receiving the test drug treatment, or the interpretation of the toxic reaction and adverse event may cause confusion;
- •It is expected to receive any other form of anti-tumor drug treatment during the study period;
- •Women in pregnancy or lactation;
- •Other investigators consider it inappropriate to participate in this study.
研究组 & 干预措施
TCR-T cells
Experimental
TCR-T cell injection
干预措施: KSH01 injection (Drug)
结局指标
主要结局
Number of participants in treatment related adverse events assessed by CTCAE v4.0
时间窗: about 3 years
To evaluate the safety and tolerance of autologous TCR-T cells in target positive solid tumor subjects.
objective remission rate
时间窗: about 3 years
To preliminarily evaluate the objective remission rate of autologous TCR-T cells in the treatment of target positive solid tumor subjects (such as esophageal cancer, gastric cancer, head and neck cancer, bladder cancer, melanoma, sarcoma, etc.).
次要结局
- Maximum tolerable dose values(about 3 years)
- Changes in tumor size and time.(about 5 years)
- Concentration of pharmacokinetic values in plasma(about 3 years)
- Concentration of cytokine level value in plasma(about 3 years)
- Concentration of biomarker value in plasma(about 3 years)
研究者
研究点 (1)
Loading locations...
相似试验
招募中
1 期
A Phase I/II Clinical Study in Patients with Advanced Solid Tumor.NCT05970016Beijing Tide Pharmaceutical Co., Ltd56
已完成
1 期
The Treatment of Patients With Type 1 Diabetes Mellitus With Autologous Tolerogenic Dendritic CellsDiabetes MellitusNCT05207995Institute of Biophysics and Cell Engineering of National Academy of Sciences of Belarus32
招募中
1 期
A Clinical Study of SHR-3276 for Injection in Patients With Advanced Malignant TumorsAdvanced Solid TumorsNCT06643754Suzhou Suncadia Biopharmaceuticals Co., Ltd.115
招募中
1 期
PE0116 and PE0105 Injection in Treatment of Patients With Advanced Solid TumorLocally Advanced/Metastatic Solid TumorsNCT05801237Shanghai HyaMab Biotech Co.,Ltd.120
终止
1 期
A Study to Assess Safety of Relatlimab With Ipilimumab in Participants With Advanced Melanoma Who Progressed on Anti-Programmed Cell Death Protein 1 (Anti-PD-1) TreatmentMelanomaNCT03978611Bristol-Myers Squibb11