Trial Title:
KSH01-TCRT Solid Tumors
NCT ID:
NCT05539833
Condition:
TCR-T Cells
Refractory Solid Tumors
Relapsed Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
KSH01 injection
Description:
TCR-T cell injection
Arm group label:
TCR-T cells
Summary:
1) Safety and efficacy of TCR-T cells in subjects with refractory/relapsed solid
tumors. 2) The activation and proliferation of TCR-T cells in the subject, and the
survival time.
Criteria for eligibility:
Criteria:
1. Inclusion Criteria:
- Voluntarily participate in clinical research; fully understand this research
and sign informed consent voluntarily; be willing to follow and have the
ability to complete all experimental procedures;
- Male or female, aged 18 to 70 years (inclusive);
- Subjects with advanced malignant solid tumors confirmed by histology or
cytology;
- Dose escalation phase: subjects who have no standard treatment, or who
have failed or relapsed after standard treatment, or who cannot tolerate
standard treatment with positive target expression;
- Dose expansion phase: target-positive subjects who progressed on
first-line therapy;
- HLA-A*02 positive and tumor target positive (target tumor cell staining
intensity is divided into 0, 1+, 2+, 3+, >30% of cancer cells express 2+ or 3+
positive positive for the target)
- All toxicities caused by previous anti-tumor therapy were relieved to grade 0-1
(according to NCI CTCAE version 5.0) or to an acceptable level for
inclusion/exclusion criteria. Except for other toxicities such as alopecia and
vitiligo that the researchers believe do not pose a safety risk to the
subjects;
- Sufficient organ function (without receiving medical support such as blood
transfusion and granulocyte colony-stimulating factor within 14 days before
cell reinfusion), defined as follows:
- Blood system:
- The neutrophil count (ANC) is not lower than the lower limit of the normal
value of the center;
- White blood cells (WBC) are not lower than the lower limit of the normal
value of the center;
- Platelet count (PLT) is not lower than the lower limit of normal value in
our center;
- Hemoglobin (Hb) not less than 0.8*LLN (lower limit of normal);
- Liver function:
- Total bilirubin (TBIL) ≤ 2.0 × upper limit of normal (ULN), Gilbert
disease subjects should be ≤ 3 × ULN;
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤3×ULN
(in the dose expansion phase, subjects with liver metastases or liver
cancer can be ≤5×ULN); alkaline phosphatase (ALP) ≤2.5× ULN (subjects with
bone metastases, ALP≤5×ULN);
- Renal function:
- 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)));
- The qualitative urine protein is ≤1+; if the qualitative urine protein is
≥2+, a 24-hour urine protein quantitative examination is required, and if
the 24-hour urine protein quantitative <1 g, it is acceptable;
- Coagulation function:
Those who did not receive anticoagulation therapy: International normalized ratio
(INR), activated partial thromboplastin time (APTT) should be less than or equal to
1.5×ULN; patients with liver metastasis or liver cancer should be less than or equal
to 2×ULN;
- Physical status: Eastern Cooperative Oncology Group (ECOG) score of 0-1;
- Expected survival period ≥ 12 weeks;
- According to RECIST 1.1 criteria, there is at least one measurable lesion (dose
expansion phase) or an evaluable lesion (dose escalation phase);
- After assessment, enough PBMC cells can be collected in the subject to prepare
autologous TCR-T cells;
- After evaluation, the prepared autologous TCR-T cells are of sufficient
quantity and qualified quality, and can be used for clinical reinfusion of the
corresponding dose;
- Female subjects with fertile potential have a negative blood pregnancy result
within 3 days before the cell reinfusion, and are willing to abstain from sex
or take medically approved high-efficiency drugs from the time of signing the
informed consent to 6 months after the end of the last medication.
contraceptive measures (eg, IUDs, condoms);
- Male subjects are willing to keep abstinence or take medically approved
high-efficiency contraceptive measures from the time of signing the informed
consent to 6 months after the end of the last medication, and do not donate
sperm during this period.
- All subjects are required to provide tumor tissue specimens that can be used
for target analysis, which must be archived specimens or fresh biopsy specimens
(bone biopsy specimens are not accepted). Only those with positive target
expression can enter the study.
2. Exclusion Criteria:
- History of severe allergic diseases, severe drug allergy (including unmarketed
test drugs), or known allergy to any component of the recommended drugs
(including pretreatment drugs) in this program;
- Those who have received coronary artery reconstruction in the past;
- Evidence of significant bleeding disorders or other significant bleeding risk:
- History of intracranial hemorrhage or intraspinal hemorrhage;
- Tumor lesions invade large blood vessels and have obvious bleeding risk;
- Thrombosis or embolism occurred within 6 months before cell reinfusion;
- Clinically significant hemoptysis or tumor hemorrhage occurred within 1 month
before cell reinfusion;
- Anticoagulant therapy for therapeutic purposes (except low molecular weight
heparin) has been used within 2 weeks before cell reinfusion;
- Antiplatelet drugs, such as aspirin (>325 mg/day), clopidogrel (>75 mg/day),
dipyridamole, ticlopidine or cilostazine, were used within 10 days before cell
reinfusion azoles, etc.;
- Received the following treatments or drugs before cell reinfusion:
- Unhealed wounds, ulcers or fractures within 28 days before cell
reinfusion;
- Inoculated with live attenuated vaccine within 28 days before cell
reinfusion;
- Received nitrosourea or mitomycin C treatment within 6 weeks before cell
infusion; received oral fluorouracil treatment 2 weeks before cell
infusion or within ●half-lives of the drug (whichever is longer) ;
- Received corticosteroids within 2 weeks before cell reinfusion, or it is
expected that corticosteroid treatment may be required during blood collection,
cell collection or cell reinfusion; except for the following cases: short time
(≤7 days), dose not higher than 10 mg/d prednisone or equivalent dose of
corticosteroids for the prevention or treatment of non-autoimmune conditions;
topical, intranasal, intraocular, intraarticular or inhaled corticosteroids;
- Known leptomeningeal metastases, or uncontrolled or symptomatic central nervous
system metastases manifested by clinical symptoms, cerebral edema, spinal cord
compression, and/or progressive growth. Subjects with a history of central
nervous system metastasis or spinal cord compression are acceptable if they
have clearly received treatment and are clinically stable after 8 weeks of
discontinuation of anticonvulsants and steroids before cell reinfusion;
- The existence of any form of primary immunodeficiency;
- There is any active autoimmune disease, or there is a history of autoimmune
disease and relapse is expected (including but not limited to: systemic lupus
erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis,
inflammatory bowel disease, need for bronchial Asthma subjects medically
intervened with dilators, except for the following: type 1 diabetes; skin
conditions not requiring systemic therapy [eg, vitiligo, psoriasis, alopecia];
hypothyroidism only receiving hormone replacement therapy; childhood Asthma in
complete remission without any intervention in adulthood; or others not
expected to relapse in the absence of external triggers);
- Within 6 months before cell reinfusion, the following conditions have occurred:
myocardial infarction, severe/unstable angina, clinically significant
arrhythmia requiring clinical intervention, cerebrovascular accident/stroke,
transient ischemic attack, Subarachnoid hemorrhage, cardiac insufficiency with
New York Heart Association (NYHA) class ≥ II;
- There is currently uncontrollable pleural, pericardial, and ascites effusion;
- Before cell reinfusion, there are:
- Congenital Long QT Syndrome
- Use of a pacemaker
- Left Ventricular Ejection Fraction (LVEF) < 50%
- QTcF interval>480 msec (QTcF=QT/(RR^0.33))
- Cardiac troponin I or T >2.0 ULN
- Poorly controlled diabetes (fasting blood glucose ≥ 13.3 mM)
- Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg and/or
diastolic blood pressure ≥ 100 mmHg);
- Forced expiratory volume in the first second (FEV1) ≤ 60% or those who
need supplemental oxygen therapy;
- Unexplained fever >38.5°C during screening or before cell reinfusion (fever due
to tumor can be included in the group as judged by the investigator);
- Known history of allogeneic organ transplantation;
- 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);
- Known severe active viral, bacterial infection, or uncontrolled systemic fungal
infection;
- Positive virological test results (HIV, CMV, HSV, HPV, EBV, syphilis);
- HBsAg positive or HBcAb positive, and HBV-DNA > 200 IU/mL; HCV-Ab positive, and
HCV-RNA higher than the detection limit of the research center;
- According to the judgment of the investigator, the underlying condition of the
subject may increase the risk of receiving the experimental drug treatment, or
cause confusion in the interpretation of the toxic reactions and adverse
events;
- Expected to receive any other form of antitumor drug treatment during the study
period;
- Women who are pregnant or breastfeeding;
- Other investigators deem it inappropriate to participate in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The first affiliated hospital of Guang Xi medical university
Address:
City:
Nanning
Zip:
530000
Country:
China
Status:
Recruiting
Contact:
Last name:
clinical trials ksh
Phone:
18994103369
Email:
ksh-clinicalt@tcrximmune.com
Start date:
August 19, 2022
Completion date:
July 31, 2027
Lead sponsor:
Agency:
TCRx Therapeutics Co.Ltd
Agency class:
Industry
Source:
TCRx Therapeutics Co.Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05539833
