BGT007H Cells for the Treatment of Refractory Digestive System Tumors

Clinical Study on the Safety and Initial Efficacy of BGT007H Cell Therapy in Patients With Recurrent/Metastatic Refractory Digestive Tract Tumors

This is an exploratory clinical study evaluating the safety and initial efficacy of BGT007H injection in the treatment of recurrent/metastatic/refractory digestive system tumors.

Study Overview

• Status: Recruiting
• Conditions: Digestive Tract Cancer
• Intervention / Treatment: Biological: BGT007H Injection

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 BGT007H cells were set with 5 dose groups that were gradually increased for treatment evaluation. The dose groups were 2.0 × 10^8cells，5.0 × 10^8cells，1.0 × 10^9cells，3.0 × 10^9cells，6.0 × 10^9cells。 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 (Estimated): 14
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Li Li, doctor; Phone Number: +86-516-85609999; Email: lily9711214@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily sign a written informed consent;
2. Age ≥18 years old, ≤70 years old, male and female;
3. Expected survival ≥ 3 months;
4. The Eastern Cancer Collaboration (ECOG) physical fitness score was 0-1;
5. Biopsy specimen or pathological wax section test (within 3 years before the signing of informed consent) : Target protein test is positive;
6. At least one measurable lesion according to RECIST v1.1 solid tumor evaluation criteria;
7. Patients with recurrent/metastatic refractory digestive tract tumors (esophageal, gastric, pancreatic, or colorectal cancer) who have previously received second-line or above standard treatment failure or intolerance;
8. It is possible to establish a vein access for simple or intravenous blood collection, and there are no other contraindications for blood cell separation;
9. having adequate organ and bone marrow function, as defined below: Blood routine examination Neutrophil count (NEU #) ≥1.0×10^9/L Platelet count (PLT) ≥80×10^9/L Hemoglobin concentration ≥90g/L Liver function: subjects without liver metastases Aspartate aminotransferase (AST) ≤2.5× Upper Limit of Normal (ULN) Alanine aminotransferase (ALT) ≤2.5× Upper Limit of Normal (ULN) Total bilirubin (TBIL) ≤1.5×ULN Liver function: Subjects with liver metastases Aspartate aminotransferase (AST) ≤5× Upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤5× Upper limit of normal (ULN) Liver function: Subjects with liver metastases or Gilbert syndrome Total bilirubin (TBIL) ≤2×ULN renal function Creatinine clearance (CCR) ≥50 mL/min Coagulation function International Standardized ratio (INR) ≤1.5×ULN Activated partial thromboplastin time (APTT) ≤1.5×ULN
10. Toxic side effects left over from previous anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.) ≤ grade 1 (CTCAE 5.0);
11. During the study period and for 6 months after the end of dosing, fertile subjects (both male and female) must use effective medical contraception. For female subjects of reproductive age, a pregnancy test should be performed within 72 hours before the first dose and the result is negative.

Exclusion Criteria:

1. Active central nervous system metastases (except those stable after treatment);
2. HIV positive, HBsAg positive, HBV DNA copy number positive (quantitative detection ≥1000cps/ml), HCV antibody positive and HCV RNA positive;
3. Patients with mental or mental illness who cannot cooperate with treatment and efficacy evaluation;
4. Subjects with severe autoimmune diseases and long-term use of immunosuppressants;
5. Active or uncontrolled infections requiring systemic treatment during the 14 days prior to enrollment;

6. Any unstable systemic disease (including but not limited to) :

   Active infections (except local infections); unstable angina pectoris; cerebral ischemia or cerebrovascular accident (within 6 months prior to screening); myocardial infarction (within 6 months before screening); Congestive heart failure (New York Heart Association [NYHA] classification ≥III); Severe arrhythmias requiring medical treatment; have a heart condition that requires treatment or uncontrolled hypertension after treatment (blood pressure > 160mmHg/100 mmHg);

7. dysfunction of important organs such as lung, brain and kidney;
8. The subject has undergone major surgery or severe trauma within 4 weeks prior to receiving cell therapy, or is expected to undergo major surgery during the study period;
9. Received any systemic chemotherapy, immunotherapy, or small molecule targeted therapy within 1-2 weeks prior to anapheresis or within 5 half-lives, whichever is shorter;
10. The subject currently has or has had other malignant tumors that cannot be cured within 3 years, except cervical carcinoma in situ or basal cell carcinoma of the skin, and other malignant tumors with disease-free survival of more than 5 years;
11. Received chimeric antigen receptor modified T cells (including CAR-T, TCR-T) within six months;
12. Graft-versus-host disease (GVHD);
13. Participants who were receiving systemic steroid therapy prior to screening and who were determined by the investigator to require long-term use of systemic steroid therapy during treatment (except for inhalation or topical use); And subjects treated with systemic steroids within 72 h prior to cell transfusion (except for inhalation or topical use);
14. Severe allergies or history of allergies;
15. Subjects requiring anticoagulation therapy;
16. Pregnant or breastfeeding women, or have a pregnancy plan within six months (for both men and women)
17. Researchers believe that there are other reasons for not being 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: BGT007H Cell Injection; This is an exploratory study of single-arm, open, modified "3+3" dose escalation. The BGT007H cell therapy group received five progressively increased dose levels (2.0× 10^8,5.0 ×10^8, 1.0× 10^9,3.0 × 10^9,6.0 ×10^9) of BGT007H cells. Each subject was observed for at least 4 weeks after cell transfusion (DLT observation period). The first two dose groups (2.0×10^8 cells and 5.0×10^8 cells) included 1 subject each, and the other three dose groups were followed by conventional "3+3" dose increments.

Biological: BGT007H Injection; BGT007H injection (d0) were infused intravenously once, and the dose group was 2.0× 10^8 cells,5.0 ×10^8 cells, 1.0× 10^9 cells,3.0 × 10^9 cells,6.0 ×10^9 cells.

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 BGT007H injection , as specified in the protocol	From day 0 to day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	The time from the onset of leukocyte apheresis to the appearance of tumor progression or death.	12 months
Cmax	The amplification of BGT007H injection in peripheral blood peaked after administration	12 months
Tmax	Number of days of peak BGT007H injection expansion after administration	12 months
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

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 (Actual): October 22, 2023
• Primary Completion (Estimated): October 20, 2026
• Study Completion (Estimated): October 20, 2027

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: recurrent/metastatic/refractory
• Other Study ID Numbers: BR-BGT-005

Drug and device information, study documents

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