A Clinical Trial of TAA06 Injection in Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Clinical Trial of TAA06 Injection in Advanced Solid Tumors

Conditions
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Malignant Melanoma, Lung Cancer, or Colorectal Cancer

Intervention / Treatment
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* Biological: TAA06 injection


Participation Criteria
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Eligibility Criteria
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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: Urea (Urea) and serum creatinine≤1.5×ULN; Left ventricular ejection fraction ≥50%; Baseline blood oxygen saturation ≥ 94%; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAA06 injection<br>T cell injection targeting B7-H3 chimeric antigen receptor | Biological: TAA06 injection<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the safety after B7-H3 chimeric antigen receptor T cells infusion (Safety) | Incidence and treatment-relativity of adverse events assessed by NCI CTCAE v5.0. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate anti-tumor activity (overall response rate) | Rate of participants achieving a complete response (CR) or partial response (PR). | 6 months | 
| To evaluate anti-tumor activity (disease control rate) | Rate of participants achieving a complete response (CR) or partial response (PR) or stable disease (PD). | 3 months | 
| To evaluate anti-tumor activity (duration of response) | 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. | About 2 years | 
| To evaluate anti-tumor activity (Progression Free Survival) | 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. | About 2 years | 
| To evaluate anti-tumor activity (overall survival) | Defined as the time from start of the random beginning to death (due to any cause). | About 2 years |