Trial Title:
KSH01-R02-101 Solid Tumors
NCT ID:
NCT05580796
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Genetic engineering of T-cells
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 tolerance
2. . objective response rate
Detailed description:
1. . To evaluate the safety and tolerance of autologous TCR-T cells in target positive
solid tumor patients.
2. . 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.)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1) 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;
-
2) Male or female, 18 to 70 years old (including boundary value);
-
3) Malignant solid tumors failed to receive standard treatment;
-
4) 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)
- 5). 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
-
6) 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；
-
7) Physical condition: The score of the Eastern American Cooperative Oncology
Group (ECOG) was 0-1;
-
8) Expected survival time ≥ 12 weeks;
-
9) According to RECIST 1.1, there is at least one measurable lesion (dose
expansion stage) or evaluable lesion (dose increase stage);
-
10) After evaluation, enough PBMC cells can be collected from the subjects to
prepare autologous TCR-T cells;
-
11) 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;
-
12) 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);
-
13) 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;
-
14) 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.
Exclusion Criteria:
-
1) 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;
-
2) Previous coronary artery reconstruction;
-
3) 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;
-
4) 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;
-
5) 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;
-
6) Presence of any form of primary immunodeficiency;
-
7) 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);
-
8) 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;
-
9) At present, there are uncontrollable pleural, pericardial and peritoneal
effusion;
-
10) 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;
-
11) 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);
-
12) History of allograft transplantation is known;
-
13) Known history of alcohol abuse, psychotropic substance abuse or drug abuse;
-
14) Have a clear history of neurological or mental disorders, such as epilepsy,
dementia, schizophrenia, etc;
-
15) Known to have acquired immunodeficiency syndrome (AIDS);
-
16) Serious active virus, bacterial infection or uncontrolled systemic fungal
infection are known;
-
17) Virology test results (HIV, CMV, HSV, HPV, EBV, syphilis) are positive;
-
18) 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;
-
19) 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;
-
20) It is expected to receive any other form of anti-tumor drug treatment during
the study period;
-
21) Women in pregnancy or lactation;
-
22) Other investigators consider it inappropriate to participate in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chinese People's Liberation Army (PLA) General Hospital
Address:
City:
Beijing
Zip:
100000
Country:
China
Status:
Recruiting
Contact:
Last name:
clinical trials ksh
Email:
ksh-clinicalt@tcrximmune.com
Start date:
October 11, 2022
Completion date:
October 11, 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/NCT05580796
