Gastrointestinal Tumors
Conditions
Brief summary
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
Main research objectives: Evaluation of the safety and tolerability of BGT007H cell therapy in patients with recurrent/refractory gastrointestinal tumors Secondary research objectives: 1. Evaluate the pharmacokinetic (PK) characteristics of BGT007H cells after reinfusion; 2. Evaluation of the initial effectiveness of BGT007H cell therapy in patients with recurrent/refractory gastrointestinal tumors Exploratory Purpose 1. Exploring the correlation between the proliferation and survival of BGT007H cells in vivo and their therapeutic effects; 2. Exploring the correlation between target expression levels and efficacy
Interventions
BIOLOGICALFirst dose
1.0×10\^8cells,Intravenous infusion，1 subject is planned to be enrolled
BIOLOGICALSecond dose
3.0×10\^8cells,Intravenous infusion，3 subject is planned to be enrolled
BIOLOGICALThe third dose
1.0×10\^9cells,Intravenous infusion，3 subject is planned to be enrolled
BIOLOGICALThe fourth dose
3.0×10\^9cells,Intravenous infusion，3 subject is planned to be enrolled
Sponsors
The First Affiliated Hospital of Zhengzhou University
BioSyngen Pte Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose | From the infusion (Day 0) to Day 28 | The maximum CAR-T dose that can be tolerated in the study. |
| Dose-Limiting Toxicity (DLT) | From the infusion (Day 0) to Day 28 | Incidence of adverse events defined as Dose-Limiting Toxicity (DLT). |
| AE, SAE, AESI, CRS, ICANS, TEAE | The day of leukapheresis to 12 months after infusion | 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). |
Countries
China
Contacts
Primary ContactXinfeng Chen
Backup ContactDan Wang
Outcome results
None listed