BGT007 Cell Treatment of Nasopharyngeal Carcinoma

Study Overview
=================
Brief Summary
-----------------
This is an exploratory study to evaluate the safety and preliminary effectiveness of BGT007 cells in the treatment of recurrent/metastatic nasopharyngeal carcinoma

Detailed Description
-----------------
The researchers designed a single arm, open, exploratory study to improve the 3+3 dose escalation. The maximum dose or the best effective dose shall be determined according to the subject and dose increasing test to verify the safe and effective number of cells per unit weight. The improved 3+3 dose increasing design was adopted, and BGT007 cells were set with 5 dose groups that were gradually increased for treatment evaluation. The dose groups were 5.0 × 10^5cells/kg，1.0 × 10^6cells/kg，3.0 × 10^6cells/kg，6.0 × 10^6cells/kg，1.0 × 10^7cells/kg。 Cell reinfusion will be carried out on day 0 (d0), and each subject will be observed for at least 4 weeks after receiving cell reinfusion (DLT observation period)

Official Title
-----------------
Clinical Study of the Safety and Initial Efficacy of BGT007 Cells in the Treatment of Patients With Relapsed /Metastatic Nasopharyngeal Carcinoma

Conditions
-----------------
Nasopharyngeal Carcinoma

Intervention / Treatment
-----------------
* Biological: BGT007 Cell Injection
* Drug: Fludarabine
* Drug: cyclophosphamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Sign the written informed consent voluntarily; 2. Age ≥ 18, ≤ 75, male or female; 3.Expected life ≥ 3 months 4. The physical condition score of the Eastern Tumor Cooperative Organization (ECOG) is 0-2; 5.Biopsy sample or pathological wax slice test (within 1 year before signing the informed consent): target test positive 6. According to RECIST v1.1 solid tumor evaluation criteria, there is at least one measurable lesion; 7. Patients with recurrent/metastatic nasopharyngeal carcinoma who have received second-line or above system treatment failure in the past (Recurrence of nasopharyngeal carcinoma: nasopharyngeal carcinoma confirmed by pathology, after radical radiotherapy, the clinical tumor disappears completely, and after 6 months of treatment, local tumors with the same pathological type as the original tumor reappear; metastasis of nasopharyngeal carcinoma: tumor cells transfer from the primary site to distant organs through various ways, such as blood and lymph, and form tumor metastasis focus); 8. It is possible to establish a single blood collection or venous blood collection channel, and there is no other blood cell separation contraindication; 9. It has sufficient organ and bone marrow functions, as defined below routine blood test Neutrophil count (NEUT #) ≥ 1.0 × 10^9/L Platelet count (PLT) ≥ 80 × 10^9/L Hemoglobin concentration ≥ 90g/L Liver function: subjects without liver metastasis Aspartate aminotransferase (AST) ≤ 2.5 × Upper limit of normal value (ULN) Alanine aminotransferase (ALT) ≤ 2.5 × Upper limit of normal value (ULN) Total bilirubin (TBIL) ≤ 1.5 × ULN Liver function: subjects with liver metastasis Aspartate aminotransferase (AST) ≤ 5 × Upper limit of normal value (ULN) Alanine aminotransferase (ALT) ≤ 5 × Upper limit of normal value (ULN) Liver function: subjects with liver metastasis or Gilbert syndrome Total bilirubin (TBIL) ≤ 2 × ULN renal function Creatinine clearance rate (CCR) ≥ 50mL/min Coagulation function International normalized ratio (INR) ≤ 1.5 × ULN Activated partial thromboplastin event (APTT) ≤ 1.5 × ULN 10. Toxic side effects left by early anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.) ≤ Level 1 (CTCAE5.0); 11. During the study period and within 6 months after the last administration, subjects with fertility (male or female) must take effective medical contraceptive measures. Female subjects of childbearing age must have a pregnancy test within 72 hours before the first administration, and the result is negative. Exclusion Criteria: 1. Active central nervous system metastasis (except those that are stable after treatment); 2. HIV positive or HBsAg positive, HBV DNA copy number is positive (quantitative test ≥ 1000 cps/ml) or HCV antibody is positive and HCV RNA is positive; 3. Those who have mental or psychological diseases and cannot cooperate with the treatment and efficacy evaluation; 4. Subjects with severe autoimmune diseases and long-term application of immunosuppressants; 5. There is active infection or uncontrollable infection requiring systemic treatment within 14 days before signing the informed consent form; 6. Any unstable systemic disease (including but not limited to): Active infection (except local infection); Unstable angina pectoris; Cerebrovascular ischemia or cerebrovascular accident (within 6 months before screening); Myocardial infarction (within 6 months before screening); Congestive heart failure (New York Heart Association [HYHA] classification ≥ Ⅲ); Serious arrhythmia requiring drug treatment; Heart disease needs treatment or hypertension is out of control after treatment (blood pressure>160mmHg/100mmHg); 7. Complicated with dysfunction of lung, brain, kidney and other important organs; 8. Subjects had undergone major surgery or severe trauma within 4 weeks before signing the informed consent form, or were expected to undergo major surgery during the study period. 9. Subjects received the last radiotherapy or anti-tumor treatment (chemotherapy, targeted therapy or immunotherapy) within 4 weeks before signing the informed consent form; 10. The subject currently suffers from or has suffered from other malignant tumors that cannot be cured within 3 years, except for cervical cancer or skin basal cell cancer, and other malignant tumors with a disease-free survival period of more than 5 years; 11. Have received T cells (including CAR-T and TCR-T) modified by chimeric antigen receptor within half a year before signing the informed consent form; 12. Graft versus host disease (GVHD) 13. Subjects who were receiving systemic steroid treatment before signing the informed consent form and who were judged by the investigator to need long-term use of systemic steroid treatment during the treatment period (except for inhalation or local use); And subjects treated with systemic steroids within 72 hours before cell reinfusion (except for inhalation or local use); 14. Serious allergy or allergy history 15. Subjects requiring anticoagulation treatment 16. Pregnant or lactating women, or have a pregnancy plan within six months (for both men and women); 17. The investigator believes that there are other reasons that cannot be included in the treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGT007 Cell Injection<br>In this study, 23 patients diagnosed with recurrent/metastatic nasopharyngeal carcinoma will receive a single intravenous infusion of BGT007 cells after enrollment, with a dose of 5.0 × 10^5cells/kg，1.0 × 10^6cells/kg，3.0 × 10^6cells/kg，6.0 × 10^6cells/kg，1.0 × 10^7cells/kg。 One subject was enrolled in each of the first two dose groups, and the other three dose groups were enrolled in accordance with the conventional 3+3 dose increase. | Biological: BGT007 Cell Injection<br>* BGT007 cells (d0) were infused intravenously once, and the dose group was 5.0 × 10^5cells/kg，1.0 × 10^6cells/kg，3.0 × 10^6cells/kg，6.0 × 10^6cells/kg，1.0 × 10^7cells/kg。<br>Drug: Fludarabine<br>* Fludarabine 25 30mg/m2/d was infused intravenously for 3 consecutive days. (- 5 days to - 3 days)<br>* Other names: FLUDARA;Drug: cyclophosphamide<br>* 250 350mg/m2/d cyclophosphamide was infused intravenously for 3 consecutive days. (- 5 days to - 3 days)<br>* Other names: Cytoxan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity（DLT） | Adverse events related to cell therapy were observed on 28 days after BGT007 cell injection , as specified in the protocol | From day 0 to day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | The amplification of BGT007 cells in peripheral blood peaked after administration | 12 months | 
| Tmax | Number of days of peak BGT007 cell expansion after administration | 12 months | 
| AUC(Day 0 to Day 28) | The area under the curve of BGT007 cells from day 0 to day 28 after administration was plotted by the visit time of BGT007 cells in peripheral blood | From day 0 to day 28 | 
| ORR | Proportion of patients who achieved pre-defined tumor volume reduction and maintained the minimum time limit.Imaging examination was performed after administration, and RECIST1.1 evaluation criteria was used for evaluation | 12 months | 
| PFS | The time from the onset of leukocyte apheresis to the appearance of tumor progression or death. | 12 months | 
| OS | The time between leukocyte apheresis and death from any cause. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CAR-T, nasopharyngeal carcinoma, recurrent/metastatic nasopharyngeal carcinoma