Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas

Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas

The aim of this clinical trial is to assess the feasibility, safety and efficacy of CAR T cells immunotherapy in patients who have sarcoma that is relapsed or late staged. Another goal of the study is to assess the safety and efficacy of the therapy that combines CAR T cells and IgT cells to treat sarcoma.

Important Regulatory Notice:

This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.

ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.

Patients with late staged and/or recurrent sarcoma have poor prognosis despite complex multimodal therapy. Therefore, novel curative approaches are needed.This study will combine two different ways to fight sarcoma: antibodies and CAR-T cells. Several immune checkpoint antibodies have been examined on various tumors with good outcomes. Sarcoma is known to express increased levels of surface antigens that can be targeted by CAR-T cells. Thus, in this study, the 4SCAR-IgT cells targeting sarcoma surface antigens will be infused in dose escalation cohorts.This study will assess the feasibility, safety, efficacy and side effects of CAR T cells immunotherapy in patients who have sarcoma that is relapsed or late staged.

Inclusion Criteria:

1. Stage Ⅲ，Ⅳ sarcoma patients or recurrent sarcoma patients;
2. Age: ≥ 18 and ≤65 years of age at the time of enrollment;
3. At least 4 weeks since any chemotherapy or radiotherapy and at least 1 week since immunosuppressive therapy such as using steroid hormone before enrollment;
4. Side effects of chemotherapy have been well managed;
5. Malignant cells are target antigen positive(higher than ++) confirmed by IHC, quantitative PCR or sequencing;
6. Karnofsky /jansky score of 50% or greater;
7. Expected survival > 6 weeks;
8. ANC≥ 1×10^6/L，PLT ≥ 1×10^8/L;
9. Pulse oximetry of≥90% on room air；
10. Adequate hepatic function,defined as aspartate aminotransferase(AST)< 5 times upper limit of normal(ULN),serum bilirubin < 3 times ULN;
11. Adequate renal function,defined as serum creatinine less than 2 times ULN,if serum creatinine more than 1.5 times ULN,creatinine clearance rate test is needed;
12. Patients must have autologous transduced T cells at levels greater than 15%;
13. Sign an informed consent and assent.

Exclusion Criteria:

1. The disease is progresseing rapidly;
2. The patient is receiving therapy of other new drugs;
3. Evidence of tumor potentially causing airway obstruction;
4. Epilepsy history or other CNS diseases;
5. Patients who need immunosuppressive drugs because of GVAD;
6. History of long QT syndrome or severe heart diseases;
7. Uncontrolled active infection;
8. Active hepatitis B virus,hepatitis C virus and HIV infection;
9. Receiving systemic corticosteroid 2 weeks before enrollment except for inhaled steroids;
10. Previous treatment with any gene therapy;
11. Creatinine>2.5mg/dl or ALT/AST>3 times normal or bilirubin>2.0 mg/dl;
12. Patients who have other uncontrolled diseases would preclude participation as outlined;
13. Pregnant or lactating women;
14. Patients previously experienced toxicity from cyclophosphamide;
15. Patients who have CNS sarcoma;
16. In condition that may bring risks to subjects or interference to clinical trials.