Trial Title:
TP53 R248Q TCR-T Cell Therapy for Advanced Solid Tumor
NCT ID:
NCT06619886
Condition:
Solid Tumor, Adult
Lung Adenocarcinoma
Pancreas Cancer
Colorectal Cancer
Other Solid Tumor
Conditions: Official terms:
Neoplasms
Pancreatic Neoplasms
Adenocarcinoma of Lung
Conditions: Keywords:
TP53-R248Q
TCR-T
advanced solid tumor
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Autologous, engineered T Cells targeting TP53 R248Q
Description:
TP53-R248Q mutant TCR-T Cells Injection, 28 days as a treatment cycle (cycle number N≤3),
each cycle was divided into three D0, D7, D14 infusion, a total of 3 dose groups were set
up, the single infusion of cells within the range of ±20% all meet the requirements
Arm group label:
TP53 R248Q specific TCR transduction T cell therapy
Summary:
To evaluate the safety and efficacy of T cell therapy with mutated TP53 R248Q specific
TCR transduction in patients with advanced solid tumor expressing the TP53 R248Q mutation
and the HLA-A*11:01 allele.
Detailed description:
Malignant tumors are a major disease threatening the health of the Chinese people, with
about 4.6 million new cancer patients and 2 million deaths each year in China. P53 gene
mutation is an important driver gene in the pathogenesis of malignant tumors. P53 gene
mutation is present in about half of cancer patients. Tumors carrying P53 gene mutation
are insensitive to treatment, have poor response, are easy to be resistant, are easy to
relapse, and have a high mortality rate. At present, there is no drug that directly
targets P53 gene mutation. Our laboratory has previously built a TCR-T cell R & D
platform. Using this platform, we have successfully developed a TCR-T cell specific
killing function for tumor cells targeting the R248Q mutation of the most common TP53
protein in hematological tumors and targeting the most high-frequency HLA-A11:01 subtype
of TCR-T cells in the Chinese population using in vitro and in vivo animal models, and
applied for a Chinese invention patent and PCT invention patent. The findings provide new
ideas and treatment methods for immune cell therapy of malignant tumors. At present, we
cooperate with the hematology clinical team of Shanghai First People's Hospital and
Shanghai Pharmaceutical Group Biotherapy Technology Co., Ltd. to prepare to carry out
investigator-initiated clinical trials.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. signed a written informed consent form (ICF), and can comply with protocol-specified
visits and related procedures;
2. aged ≥ 18 years, and ≤ 75 years, male or female;
3. Subject must be pathologically confirmed with one of the histology below:
Lung carcinoma Colorectal adenocarcinoma Pancreatic adenocarcinoma Any other solid
tumor (progression after receiving standard treatment);
4. subjects with TP53R248Q mutation in genetic testing, as determined by DNA or RNA
sequencing methods;
5. if patients with brain metastases are asymptomatic and less than 3 brain lesions
less than 3 cm in diameter, they may be eligible;
6. ECOG score 0-1;
7. Expected survival of no less than 12 weeks;
8. According to RECISTv1.1 and mRECIST, subjects have at least 1 measurable lesion
(lesions that have received local therapy such as radiotherapy and interventional
therapy cannot be used as measurable lesions unless imaging evidence confirms that
the lesion has clearly progressed), RECISTv1.1 is non-lymph node lesions with the
longest diameter ≥ 10 mm on CT or MRI, and/or lymph node lesions with the short
diameter ≥ 15 mm; mRECIST is non-lymph node measurable lesion criteria that meet
RECISTv1.1 criteria, and showed intratumoral arterial enhancement in enhanced CT or
MRI;
9. subjects should provide fresh tumor tissue samples that meet the requirements or
within 2 years before signing the ICF;
10. Adequate organ and bone marrow function as defined by the following laboratory
criteria: (1) bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
platelet (PLT) ≥ 75 × 109/L (transfusion or hematopoietic stimulating factor not
acceptable within 14 days prior to Screening); (2) hemoglobin ≥ 90 g/L; (3) liver
function: total bilirubin ≤ 2.5 × ULN; alanine aminotransferase ≤ 5 × ULN; aspartate
aminotransferase ≤ 5 × ULN; (4) renal function: serum creatinine ≤ 1.5 × ULN, or
creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); (5)
coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, activated
partial thromboplastin time (APTT) ≤ 1.5 × ULN (INR between 2.0 and 3.0 is required
for subjects receiving prophylactic anticoagulant therapy);
11. Males of childbearing potential and females of childbearing potential must agree to
use effective contraception from signing the ICF until one year after the last cell
infusion and females of childbearing potential must have a negative blood pregnancy
test at screening.
Exclusion Criteria:
1. previous bone marrow or organ transplantation (including but not limited to liver
transplantation) or waiting for transplantation;
2. previous or concurrent history of other malignancies (cured and at least 2 years
before screening without recurrence of cervical carcinoma in situ, non-invasive
basal cell or squamous cell skin cancer or radical treatment of local prostate
cancer, radical resection of ductal carcinoma in situ can be enrolled in the study);
3. hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive
and HBV DNA > 500 IU/mL (lower limit of detection < HBV DNA ≤ 500 IU/mL, clear
lymphocyte conditioning medication before the need for at least 14 days of antiviral
therapy and continuous antiviral therapy during the study can be enrolled);
hepatitis C virus (HCV) antibody positive and HCV RNA positive; human
immunodeficiency virus (HIV) antibody positive; syphilis antibody positive;
4. HLA antibody positive subjects, including weak positive, positive and strong
positive (those with different HLA typing sites from TP53R248QTCR-T cell injection
can be enrolled in the study);
5. previous treatment with other cell products or TP53 targeted drugs;
6. treatment with any fluorouracil chemotherapeutic drugs or small molecule targeted
drugs within 14 days or 5 half-lives (whichever is shorter) before screening, and
any antineoplastic biological agents or non-fluorouracil chemotherapeutic agents;
radical radiotherapy or extensive radiotherapy within 28 days before screening
(except palliative radiotherapy for non-target lesions performed locally to relieve
symptoms); traditional Chinese medicine/Chinese herbal medicine and local
interventional therapy with antineoplastic indications within 14 days before
screening;
7. adverse events caused by previous antineoplastic therapy have not yet recovered to
grade 1 or baseline levels, except for alopecia, grade 2 peripheral neurotoxicity,
and hypothyroidism stabilized by hormone replacement therapy;
8. live attenuated vaccination within 28 days before screening, or live attenuated
vaccination during the study;
9. major surgical treatment (except liver mass biopsy) within 28 days before screening,
or major surgical treatment during the study;
10. Requirement for chronic systemic corticosteroids (at doses ≥ 10 mg/day prednisone or
equivalent) or other immunosuppressive medication within 14 days prior to the first
study drug infusion or during the study, with the exception of inhaled or topical
use;
11. Subjects with fungal, bacterial, viral, tuberculosis or other infection requiring
systemic anti-infective therapy within 14 days prior to screening;
12. Patients with active or previous autoimmune diseases that may relapse, such as
systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vasculitis, psoriasis, etc.;
13. Previous or current interstitial lung disease, dust disease, radiation pneumonitis,
severely impaired pulmonary function and other conditions;
14. Third space effusion that is not clinically well controlled before screening, such
as pleural effusion and ascites that cannot be controlled by drainage or other
methods;
15. History of serious cardiovascular and cerebrovascular diseases, including but not
limited to:
- severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia
requiring clinical intervention, grade II-III atrioventricular block, etc.;
- prolonged QT interval corrected by Fridericia formula (QTcF), > 450 ms in
men and > 470 ms in women;
- acute coronary syndrome, congestive heart failure, aortic dissection, stroke or
other ≥ Grade 3 cardiovascular and cerebrovascular events within 6 months
before screening;
- presence of heart failure with New York Heart Association (NYHA) functional
class ≥ II or left ventricular ejection fraction (LVEF) < 50%;
- clinically uncontrolled hypertension, systolic blood pressure ≥ 160 mmHg and/or
diastolic blood pressure ≥ 100 mmHg.
16. Patients with a history of pulmonary embolism or severe lower extremity deep venous
thrombosis, need to undergo inferior vena cava filter placement and other
interventional therapy or need to use therapeutic doses of anticoagulants during
screening;
17. Subjects are participating in other interventional clinical studies;
18. Pregnant or lactating women;
19. Researchers believe that subjects have other conditions that may affect compliance
or are not suitable for participating in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Oncology, Shanghai General Hospital
Address:
City:
Shanghai
Zip:
200080
Country:
China
Contact:
Last name:
Haiyan Zhang, Dr.
Phone:
18930220751
Email:
13611956117@163.com
Start date:
September 24, 2024
Completion date:
October 31, 2027
Lead sponsor:
Agency:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Agency class:
Other
Source:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06619886
