a clinical trial of taa06 injection in advanced solid tumors

Conditions: Malignant Melanoma, Lung Cancer, or Colorectal Cancer

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.


Eligibility criteria:
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.