bgt007h cells for the treatment of recurrent/refractory gastrointestinal tumors

Conditions: Gastrointestinal Tumors

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.

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.