Safety and Efficacy of Chimeric Antigen Receptor T Lymphocytes for Patients With Intermediate and Advanced Tumors

Study Overview
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Brief Summary
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This was a single arm, open-label, single center, cohort study to determine the efficacy and safety of AMT-116 CAR-T cells in patients with moderate or far advanced non-small cell lung carcinoma (NSCLC) and squamous cell cancer of the head and neck (HNSCC)，AMT-253 CAR-T cells in patients with moderate or far advanced melanoma.

Official Title
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Safety and Efficacy of Chimeric Antigen Receptor T Lymphocytes for Patients With Intermediate and Advanced Tumors

Conditions
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Melanoma, Non-small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Biological: AMT-116 CAR-T cells
* Biological: AMT-253 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years old, both men and women, and the survival period is more than 6 months. At least one assessable focus, failure of previous multi-line treatment or stable condition after treatment. Patients with melanoma confirmed by histopathology, patients with non-small cell lung cancer(squamous carcinoma) and head and neck squamous cell carcinoma. The surgically removed pathological tissue can be used for immunohistochemical detection of target protein (paraffin section should be within 5 years), and the positive expression of target protein in line with pathological diagnosis (immunohistochemical staining + + or + + +). Sufficient venous access for blood sampling and venous blood sampling, no contraindications for lymphocyte collection. Routine blood examination: white blood cell count (WBC) ≥ 3 × 10^9 / L, lymphocyte count (ly) ≥ 0.8 × 10^9 / L, hemoglobin (HB) ≥ 90g / L, platelet (PLT) ≥ 80 × 10^9/L. Liver and kidney function: alanine aminotransferase and aspartate aminotransferase < 3 ULN, total bilirubin (TBIL) < 1.5 ULN, serum creatinine (SCR) < 2 ULN. The subjects voluntarily joined the study, signed the informed consent form, had good compliance and cooperated with the follow-up. Exclusion Criteria: Active hepatitis B or hepatitis C virus, HIV infection, or other unhealed active infections. Patients with second tumor. Patients previously treated with car-t cells. Requiring long-term use of immunosuppressants for any reason. Any serious and uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease and temporal arteritis. Subjects with severe heart, lung, liver and kidney dysfunction or severe lung diseases. Current systemic use of steroid cells (except for recent or current use of inhaled steroids). Pregnant and lactating subjects. Allergic to immunotherapy and related cells. Subjects with a history of organ transplantation or waiting for organ transplantation. After evaluation, the investigator considered that the subjects were unable or unwilling to comply with the requirements of the study protocol.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NSCLC/HNSCC：AMT-116 CAR-T cells<br>Patients with moderate or far advanced non-small cell lung carcinomav or head and neck Squamous Cell Carcinoma. | Biological: AMT-116 CAR-T cells<br>* Classical 3+3 dose escalation will be applied to 9 subjects with moderate or far advanced non-small cell lung carcinoma (NSCLC) enrolled. Classical 3+3 dose escalation will be applied to 9 subjects with moderate or far advanced head and neck Squamous Cell Carcinoma (HNSCC) enrolled.<br>|
| Experimental: MEL：AMT-253 CAR-T cells<br>Patients with moderate or far advanced melanoma. | Biological: AMT-253 CAR-T cells<br>* 1.The classic 3 + 3 dose escalation will be applied to 9 selected subjects with moderate or far advanced melanoma by intravenous drip. 2.3   6 patients with intermediate and advanced melanoma will be injected intratumorally at a dose of ≤ 1 × 10^8 cells. 3.3   6 patients with operable advanced melanoma will be treated with postoperative adjuvant treatment at a dose of ≤ 1 × 10^8 cells ≤ intravenous drip on Day 1 of each 42 days cycle (8 cycle maximum).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | 24 weeks | 
| Overall Response Rate (ORR) |  | 24 weeks | 
| One year recurrence rate |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival(PFS) |  | 24 weeks | 
| Relapse Free Survival(RFS) |  | 24 weeks |