Malignant Melanoma, Lung Cancer, or Colorectal Cancer
Conditions
Brief summary
B7-H3 (also known as CD276) is widely expressed on the surface of a variety of malignancies solid tumors, while it rarely or even doesn't express on normal tissues. Therefore, B7-H3 is an ideal target for chimeric antigen receptor (CAR) T cells therapy. TAA06 injection is a CAR T injection targeting B7-H3. This is a phase I clinical study with the primary objective of evaluating the safety and tolerability of TAA06 injection in subjects with TAA06-positive advanced solid tumors. The secondary objectives are as follows: to evaluate the distribution, proliferation and persistence of B7-H3-targeted CAR T cells after injection of TAA06 in subjects; to preliminarily evaluate the efficacy of TAA06 injection in subjects with TAA06-positive advanced solid tumor.
Interventions
BIOLOGICALTAA06 injection
The subjects, who sign the informed consent forms and been screened by inclusion/exclusion criteria, will be treated with 1×106\ 1×108 CAR-T/kg. And the subjects will be administered once.
Sponsors
Hebei Medical University Fourth Hospital
PersonGen BioTherapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* (1) Aged 18 to 70 years old (inclusive), male or female; * (2) Expected survival time ≥ 12 weeks; * (3) ECOG performance status of 0-1; * (4) It is clearly diagnosed by pathology to be any of the following tumor types: malignant melanoma, lung cancer or colorectal cancer, and the positive rate of TAA06 expression in tumor tissues is ≥1% after immunohistochemical detection; * (5) Subjects whose standard treatment methods are ineffective (eg: relapse after surgery, disease progress after treatment with chemotherapy, radiotherapy or targeted drugs); * (6) According to the curative effect evaluation standard for solid tumors (RECIST 1.1), at least one measurable lesion (the longest diameter of the solid lesion ≥ 10mm, or the short diameter of the lymph node lesion ≥ 15mm); * (7) The main organ function is normal (white blood cell count ≥3×109/L, neutrophil count ≥1.5×109/L, hemoglobin ≥8.5g/dL, platelet count ≥80×109/L, lymphocyte count at 1×109/L (inclusive) \ 4×109/L (inclusive)); * (8) Liver and kidney function, heart and lung function meet the following criteria: 1. Urea (Urea) and serum creatinine≤1.5×ULN; 2. Left ventricular ejection fraction ≥50%; 3. Baseline blood oxygen saturation ≥ 94%; 4. Total bilirubin≤1.5×ULN; ALT and AST≤2.5×ULN; * (9) The subjects or his legal representative can fully understand the significance and risks of this trial and has signed informed consents.
Exclusion criteria
* (1) Subjects with a history of immunodeficiency or autoimmune diseases (including but not limited to rheumatoid joint disease, systemic lupus erythematosus, vasculitis, multiple sclerosis, insulin-dependent diabetes, etc.); with graft-versus-host disease (GVHD) , Or those who need to use immunosuppressive agents; * (2) Subjects with other type of malignant tumors within 5 years prior to screening; * (3) Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA titer detection not within the normal reference range; positive for hepatitis C virus (HCV) antibody and peripheral blood hepatitis C virus (HCV) RNA; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis test; * (4) Severe heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ III), severe arrhythmia; * (5) Unstable systemic diseases judged by the investigator: including but not limited to serious liver, kidney or metabolic diseases requiring drug treatment; * (6) Within 7 days prior to screening, there are active or uncontrollable infections requiring systemic therapy (except for mild genitourinary infection and upper respiratory tract infection); * (7) Pregnant or lactating women, and female subjects who plan to become pregnant within 1 year after cell infusion or male subjects whose partners plan to become pregnant within 1 year after cell infusion; * (8) Subjects who have received CAR-T therapy or other gene-modified cell therapy prior to screening; * (9) Subjects who are receiving systemic steroid therapy within 7 days prior to screening or need long-term use of systemic steroid therapy during treatment as judged by the investigator (except for inhalation or topical use); * (10) Subjects with more than a moderate amount of ascites, or after conservative medical treatment (such as diuresis, sodium restriction, excluding ascites drainage) for 2 weeks, the ascites still shows a progressive increase; * (11) Conditions not eligible for cell preparation as judged by the investigator; * (12) Other conditions considered unsuitable for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the safety after B7-H3 chimeric antigen receptor T cells infusion (Safety) | 3 months | Incidence and treatment-relativity of adverse events assessed by NCI CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate anti-tumor activity (overall response rate) | 6 months | Rate of participants achieving a complete response (CR) or partial response (PR). |
| To evaluate anti-tumor activity (disease control rate) | 3 months | Rate of participants achieving a complete response (CR) or partial response (PR) or stable disease (PD). |
| To evaluate anti-tumor activity (duration of response) | About 2 years | Defined as the time from the first tumor assessment of CR or PR to the first assessment of disease progression (PD) or death from any cause. |
| To evaluate anti-tumor activity (Progression Free Survival) | About 2 years | Defined as the time from the date of study enrollment to the time when the investigator judges that imaging disease progression or death from any cause occurs. |
| To evaluate anti-tumor activity (overall survival) | About 2 years | Defined as the time from start of the random beginning to death (due to any cause). |
Countries
China
Contacts
Primary ContactZhiyu Wang, Doctor
Outcome results
None listed