BGT007 Cell Treatment of Nasopharyngeal Carcinoma

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

This is an exploratory study to evaluate the safety and preliminary effectiveness of BGT007 cells in the treatment of recurrent/metastatic nasopharyngeal carcinoma

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Biological: BGT007 Cell Injection; Drug: Fludarabine; Drug: cyclophosphamide

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)

• Study Type: Interventional
• Enrollment (Anticipated): 23
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Yang Wu; Phone Number: +86-516-83355832; Email: claude134134@126.com
      • Contact: Liantao Li; Phone Number: +86-516-83355832; Email: liliantao@xzhmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BGT007 Cell Injection; 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; 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。; Drug: Fludarabine; Fludarabine 25~30mg/m2/d was infused intravenously for 3 consecutive days. (- 5 days to - 3 days); Other Names: FLUDARA; Drug: cyclophosphamide; 250~350mg/m2/d cyclophosphamide was infused intravenously for 3 consecutive days. (- 5 days to - 3 days); 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

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Xuzhou Medical University
• Collaborators: Guangzhou Bioresette Biomedical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 30, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 30, 2022
• First Submitted That Met QC Criteria: November 7, 2022
• First Posted (Actual): November 15, 2022

Study Record Updates

• Last Update Posted (Actual): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T; nasopharyngeal carcinoma; recurrent/metastatic nasopharyngeal carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: BR-BGT-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No