BGT007H Cells for the Treatment of Recurrent/Refractory Gastrointestinal Tumors

Study Overview
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Brief Summary
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This study is an exploratory single-arm, open, modified 3+3 dose escalation study with BGT007H injection. Approximately 11 to 14 subjects with recurrent/refractory gastrointestinal tumors will be enrolled to evaluate the safety of BGT007H injection. Four dose levels were designed for this study: 1.0×10^8cells, 3.0×10^8cells, 1.0×10^9cells, and 3.0×10^9cells. The primary objective of this study was to evaluate the safety, tolerability and pharmacokinetic profile of BGT007H cell therapy in patients with recurrent/refractory digestive tract tumors, to determine the maximum tolerated dose or the best effective dose, and to initially evaluate the effectiveness of BGT007H cell products.

Detailed Description
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Main research objectives: Evaluation of the safety and tolerability of BGT007H cell therapy in patients with recurrent/refractory gastrointestinal tumors Secondary research objectives: Evaluate the pharmacokinetic (PK) characteristics of BGT007H cells after reinfusion; Evaluation of the initial effectiveness of BGT007H cell therapy in patients with recurrent/refractory gastrointestinal tumors Exploratory Purpose Exploring the correlation between the proliferation and survival of BGT007H cells in vivo and their therapeutic effects; Exploring the correlation between target expression levels and efficacy

Official Title
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Clinical Study on the Safety and Preliminary Efficacy of BGT007H Cell Therapy in Patients With Recurrent/Refractory Gastrointestinal Tumors

Conditions
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Gastrointestinal Tumors

Intervention / Treatment
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* Biological: First dose
* Biological: Second dose
* Biological: The third dose
* Biological: The fourth dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Resources sign written informed consent; 2, age ≥18, male and female can; 3. Expected survival ≥3 months; 4. The Eastern Cancer Collaboration (ECOG) physical status score was 0-1; 5. Biopsy specimen or pathological wax section test (within 3 years before accepting the signed informed consent) : positive target test; 6. According to RECISTv1.1 solid tumor evaluation criteria, there is at least one measurable lesion; 7. Patients with advanced gastrointestinal tumors (esophageal cancer, gastric cancer, pancreatic cancer or colorectal cancer, etc.) who have been diagnosed by histology/cytology as having failed the standard of second-line or above treatment or are not suitable for/refuse to accept the standard treatment or cannot tolerate the standard treatment; The definition of intolerance: according to CTCAE V5.0, the occurrence of ≥Ⅳ hematological toxicity or ≥Ⅲ non-hematological toxicity or ≥Ⅱ damage to the heart, liver, kidney and other important organs during treatment; Treatment failure is defined as disease progression (PD) during treatment or recurrence after the end of treatment (including postoperative recurrence); 8, can establish monopexy or venous blood collection venous access, and there are no other contraindications for blood cell separation; 9, with adequate organ and bone marrow function; 10. 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 metastasis (except stable after treatment); 2, HIV positive, HBsAg positive simultaneously detected HBV DNA copy number positive (quantitative detection ≥1000cps/ml), HCV antibody positive and HCV RNA positive; 3, mental or mental illness can not cooperate with treatment and efficacy evaluation; 4. Subjects with severe autoimmune diseases and long-term use of immunosuppressants; 5. Active or uncontrollable infection requiring systemic treatment within 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 prior to screening) Congestive heart failure (New York Heart Association [NYHA] classification ≥Ⅲ; Severe arrhythmias requiring medical treatment; Have heart disease that requires treatment or uncontrolled hypertension after treatment (blood pressure > 160mmHg/100mmHg); 7, combined with lung, brain, kidney and other important organ dysfunction; 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 or 5 half-lives (whichever is shorter) before anapheresis; 10. The subject currently has or has had other malignant tumors that cannot be cured within 3 years, except cervical cancer or basal cell carcinoma of the skin, and other malignant tumors with a disease-free survival of more than 5 years; 11, received chimeric antigen receptor modified T cells (including CAR-T, CTT-T) treatment within half a year; 12. Combined graft-versus-host disease (GVHD) 13. Subjects 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 hours prior to cell transfusion (except for inhalation or topical use); 14. Severe allergy or history of allergy; 15. Subjects requiring anticoagulation therapy; 16, pregnant or breastfeeding women, or six months within the pregnancy plan (unisex; 17. Researchers believe that there are other reasons for not being included in the treatment.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGT007H injection<br>Intravenous infusion | Biological: First dose<br>* 1.0×10^8cells,Intravenous infusion，1 subject is planned to be enrolled<br>Biological: Second dose<br>* 3.0×10^8cells,Intravenous infusion，3 subject is planned to be enrolled<br>Biological: The third dose<br>* 1.0×10^9cells,Intravenous infusion，3 subject is planned to be enrolled<br>Biological: The fourth dose<br>* 3.0×10^9cells,Intravenous infusion，3 subject is planned to be enrolled<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicity (DLT) | Incidence of adverse events defined as Dose-Limiting Toxicity (DLT). | From the infusion (Day 0) to Day 28 | 
| Maximum tolerated dose | The maximum CAR-T dose that can be tolerated in the study. | From the infusion (Day 0) to Day 28 | 
| AE, SAE, AESI, CRS, ICANS, TEAE | The incidence of adverse events (AE), serious adverse events (SAE), adverse events of special interest (AESI), cytokine release syndrome (CRS) immune cell associated neurotoxicity syndrome (ICANS) and treatment-emergent adverse events (TEAE). | The day of leukapheresis to 12 months after infusion |