Clinical trial NCT06152757: BGT007H Cells for the Treatment of Recurrent/Refractory Gastrointestinal Tumors
Official title: Clinical Study on the Safety and Preliminary Efficacy of BGT007H Cell Therapy in Patients With Recurrent/Refractory Gastrointestinal Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Gastrointestinal Tumors
Lead sponsor: BioSyngen Pte Ltd
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Zhengzhou University
First posted: 2023-12-01
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-Limiting Toxicity (DLT)
timeFrame: From the infusion (Day 0) to Day 28
measure: Maximum tolerated dose
timeFrame: From the infusion (Day 0) to Day 28
measure: AE, SAE, AESI, CRS, ICANS, TEAE
timeFrame: The day of leukapheresis to 12 months after infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Yi Zhang
role: PRINCIPAL_INVESTIGATOR
References: