Safety and Efficacy of CT0494BCP in Participants With Advanced Gastric/Esophagogastric Junction Adenocarcinoma

Prior treatment

• Received anti-tumor treatment for the disease under study within 2 weeks prior to CLL, including but not limited to surgery, systemic chemotherapy (or within 5 half-lives of the drug, whichever is shorter), radiotherapy, intervention, etc., or received anti-PD-(L) 1 monoclonal antibody therapy or CLDN18.2 targeted therapy or other non-marketed clinical trial drugs within 4 weeks prior to CLL (or within 5 half-lives of the drug, whichever is shorter);
• Ongoing use of glucocorticoids within 7 days prior to CLL. Recent or current use of inhaled or topical dermal glucocorticoids and physiologic replacement therapy doses of glucocorticoids were not excluded;
• Vaccination with live attenuated vaccines within 4 weeks prior to CLL or planned during the trial;
• Previously received any genetic engineering modified cell therapy (including CAR-T, TCR-T cells, etc.);
• Participants who require anticoagulation therapy such as warfarin or heparin;
• Participants who are receiving or anticipate the need to receive long-term antiplatelet therapy during the trial;
• Abdominal/pleural effusion with clinical symptoms or requiring special treatment, such as repeated drainage, abdominal/pleural drug perfusion, etc. (participants with small amount of ascites/pleural effusion that can be detected by imaging examination or controllable as assessed by the investigator can be considered for enrollment);
• Participants who have had major surgery or significant trauma within 4 weeks prior to CLL, or anticipate the need for major surgery during the trial;

Other illness

• HIV, Treponema pallidum, HCV serology positive (HCV antibody positive but HCV-RNA negative can be included), Epstein-Barr virus (EBV) DNA (plasma or whole blood) positive, cytomegalovirus (CMV) DNA positive;
• Participants with known active autoimmune disease, including but not limited to psoriasis or rheumatoid arthritis, or other conditions requiring chronic use of immunosuppressive therapy;
• Participants with high risk of bleeding or perforation, such as deep and large ulcer in primary lesion, or anastomotic recurrence with full-thickness tumor invasion, or tumor lesion invasion into large vessels, as detected by CT/MRI or combined with gastroscopy;
• Participants with current unstable or active ulcers, active gastrointestinal bleeding, or a history of major gastrointestinal bleeding within 3 months;
• Participants with a history of organ transplantation or who are awaiting organ transplantation;
• Participant has signs of central nervous system disease or clinically significant abnormal neurological examination results or psychiatric disorders;
• Patients with other incurable malignant tumors in the past 3 years or at the same time, except for cervical cancer in situ, skin basal cell carcinoma and other very low-grade tumors.

Lab values

• Any uncontrolled active infection, including but not limited to active tuberculosis, HBV infection (including HBsAg positive, or HBcAb positive with HBV DNA above the lower limit of the laboratory test in our center), and other bacterial, viral or fungal infections requiring drug treatment. Participants who use drugs to prevent infection and can continue the trial as judged by the investigator;
• Clinically significant abnormal thyroid function as judged by the investigator (serum thyroid hormone determination includes at least FT3, FT4 and serum thyroid stimulating hormone TSH), but patients with hypothyroidism whose disease is under stable control as assessed by the investigator can enter the trial;
• Toxic reactions caused by previous treatment have not recovered to CTCAE v6.0 ≤ Grade 1, except for alopecia and other tolerable events as judged by the investigator or laboratory abnormalities allowed in this trial;
• Previous allergies to immunotherapy, tocilizumab, cyclophosphamide, fludarabine or nab-paclitaxel and other related drugs, allergies to components of CT0494BCP such as albumin, DMSO or other severe allergies;
• Other conditions not suitable for participation in this trial as assessed by the investigator prior to CLL, including but not limited to: Poorly controlled diabetes with severe complications, poorly controlled hypertension (blood pressure \> 160 mmHg/100 mmHg), hypertension requiring vasopressor drugs or symptomatic hypotension, cardiac insufficiency (including left ventricular ejection fraction \[LVEF\] \< 50%), myocardial infarction within the past 6 months, arrhythmia or unstable angina poorly controlled by drug therapy, pulmonary embolism, severe chronic obstructive pulmonary disease, interstitial lung disease, clinically significant abnormal pulmonary function test, gastrointestinal obstruction or perforation within the past 3 months, severe inflammatory state (e.g. Increased neutrophils and/or C-reactive protein); Medical discussion with the sponsor is recommended if necessary;

Other

• Pregnant or lactating females;
• Known HER2-positive (defined as IHC3 +, or IHC2 + with amplification by FISH);
• Presence of known or suspected central nervous system metastases;
• Central type or extensive lung metastasis, or extensive liver metastasis, or extensive bone metastasis;
• The longest diameter of a single target lesion \> 4 cm before CLL (lymph node lesion is short axis);
• Inability or unwillingness of the participant to comply with the protocol requirements as assessed by the investigator;
• Blood oxygen saturation ≤ 95% (finger oxygen detection method is accepted, without oxygen inhalation);

• Volunteer to participate in the clinical trial; I fully understand and are informed of this trial and sign the informed consent form; Willing to follow and able to complete all trial procedures; Age 18-70 years (inclusive), male or female; Participants with pathologically confirmed advanced gastric/esophagogastric junction adenocarcinoma; Failed at least second-line treatment (if the first-line treatment includes three drugs including taxanes \[or anthracyclines\], platinum and fluoropyrimidines, the participants can also be enrolled into the trial as eligible as assessed by the investigator); Participant's tumor tissue sample is CLDN18.2 positive by immunohistochemistry (IHC) staining (expression intensity ≥ 2 + and% positive tumor cells ≥ 40%); Estimated survival \> 12 weeks; Measurable tumor lesions according to RECIST v1.1; ECOG performance status 0 \~ 1;
• Unless otherwise specified, participants should meet the following criteria before clearing the lymphoma (local laboratory results that do not meet the following criteria are allowed to perform a re-examination within one week; if they still do not meet the criteria, they cannot clear the lymphoma):
• Blood routine: neutrophil (NE) ≥ 1.5 × 109/L, lymphocyte (LY) 0.5 × 109/L, platelet (PLT) ≥ 75 × 109/L, hemoglobin (Hb) ≥ 9.0 g/dL (no transfusion, platelet transfusion, cell growth factor \[except recombinant erythropoietin\] and other supportive treatment within 14 days before detection); Blood biochemistry: endogenous creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin ≤ 2 × ULN; Serum lipase and amylase ≤ 2 × ULN; Alkaline phosphatase ≤ 2.5 × ULN; AST, ALT and alkaline phosphatase ≤ 5 × ULN if there is bone metastasis or liver metastasis; Prothrombin time (PT) prolongation ≤ 4 s. 10. Female participants of childbearing potential must have a negative serum pregnancy test at screening and be willing to use a highly effective and reliable method of contraception for 1 year after the last dose of study treatment. The available methods are: bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusion; Or approved oral, injected or implanted hormonal methods of birth control; Or barrier contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; Male participants who are sexually active with a female of childbearing potential who have not had a vasectomy must agree to use a barrier method of birth control, such as a condom with spermicidal foam/gel/film/cream/suppository, or to use a contraceptive method for their partner (see Inclusion Criterion # 10). All men absolutely refrain from donating sperm for 1 year after the last dose of study treatment.