Clinical Study of CBG131 CAR-T Cell Injection for the Treatment of CLDN18.2-Positive Advanced Gastric and Pancreatic Cancer

Prior treatment

• Active bacterial or fungal infection within 72 h before lymphodepletion. Subjects receiving prophylactic antibiotics, antifungals or antivirals are allowed if there is no evidence of active infection and the agents are not on the prohibited-medication list.
• Systemic corticosteroids equivalent to \> 15 mg/day prednisone within 2 weeks before leukapheresis (inhaled or topical steroids permitted). Any systemic glucocorticoids within 7 days before leukapheresis, except inhaled or topical preparations.
• Live-attenuated vaccine within 4 weeks before leukapheresis or planned during the study.
• Anti-cancer therapy within 2 weeks before leukapheresis (or 5 half-lives, whichever is shorter), including surgery, systemic chemotherapy, radiotherapy, interventional procedures, or anti-PD-1/PD-L1 monoclonal antibody (mAb)/Claudin18.2-targeted agents/other investigational drugs within 4 weeks (or 5 half-lives).
• Prior gene-engineered cellular therapy (e.g. CAR-T, TCR-T, TIL).
• Major surgery within 4 weeks before leukapheresis or significant trauma, or anticipated major surgery during the study (except cataract or local-anaesthetic procedures).
• Chronic antiplatelet therapy at doses exceeding aspirin 100 mg/day or clopidogrel 75 mg/day.
• Symptomatic ascites or ascites requiring repeated paracentesis or intraperitoneal therapy; small-volume radiologic ascites permitted if asymptomatic.

Other illness

• History of organ transplantation or on transplant waiting list.
• Deep ulceration of primary tumor, full-thickness infiltration at anastomotic recurrence, or tumor encasing/invading major vessels on CT/MRI ± endoscopy, carrying high risk of bleeding or perforation.
• Clinically significant CNS disease, abnormal neurologic findings, or psychiatric disorder.
• Other malignancies within 5 years (except adequately treated cervical carcinoma in situ or basal-cell skin cancer).
• Active autoimmune disease (e.g. psoriasis, RA) or any condition requiring chronic immunosuppressive therapy.
• Any other condition that, in the opinion of the investigator, renders the subject unsuitable for participation.

Lab values

• Positive HBsAg or HBcAb with HBV-DNA ≥ ULN; positive HCV antibody with detectable HCV RNA; positive HIV antibody; positive syphilis serology.
• Prior hypersensitivity to immunotherapy, cyclophosphamide, fludarabine, albumin-bound paclitaxel, tocilizumab, or any component of CBG131 (e.g. DMSO), or other significant allergic history.
• Uncontrolled or serious illnesses that could limit participation, including: Diabetes with HbA1c \> 8%, uncontrolled hypertension (\> 160/100 mmHg), Left Ventricular Ejection Fraction (LVEF) \< 50%, congestive heart failure, acute MI, severe arrhythmia, unstable angina within 6 months, pulmonary embolism, COPD, ILD, clinically significant pulmonary-function abnormalities; Active peptic ulcer, active GI bleeding, bleeding diathesis, major GI bleed within 3 months, prior immunotherapy-related bleeding, hypotension requiring vasopressors.
• Toxicities from prior therapies not resolved to ≤ Grade 1 or baseline (except alopecia, pigmentation, or laboratory abnormalities allowed by protocol) at informed-consent signature.

Other

• Pregnant or lactating women.
• Known or suspected brain metastases.
• Portal-vein tumor thrombus or tumor thrombus in mesenteric/inferior vena cava on imaging.
• Central or extensive pulmonary metastases, extensive liver metastases, or widespread bone metastases.
• Requirement for warfarin or heparin anticoagulation.
• Clinically relevant thyroid dysfunction (TT4, TT3, FT3, FT4, TSH outside normal limits per investigator).
• Known or suspected CNS metastases.
• Single target lesion \> 4 cm in longest diameter (or \> 4 cm short axis for lymph nodes) before leukapheresis.

• Age 18-70 years (inclusive) at the time of informed consent; sex unrestricted.
• Voluntary participation: the subject (or legally authorized representative) must provide written informed consent (ICF, Informed Consent Form).
• Histologically confirmed advanced gastric or gastroesophageal junction adenocarcinoma that has progressed after ≥ 2 prior systemic regimens, OR histologically confirmed advanced pancreatic adenocarcinoma that has progressed after ≥ 1 prior systemic regimen.
• CLDN18.2 positivity in archival or fresh tumor tissue by immunohistochemistry (IHC): ≥ 40% of tumor cells staining ≥ 2+.
• At least one measurable lesion per RECIST 1.1 (longest diameter ≥ 10 mm).
• Estimated life expectancy \> 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Adequate organ function within 14 days prior to leukapheresis, defined by all of the following:
  • (1) Total bilirubin ≤ 2 × ULN (Upper Limit of Normal); (2) ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN if liver or bone metastases are present); (3) Calculated creatinine clearance (Cockcroft-Gault) ≥ 50 mL/min; (4) Hemoglobin ≥ 90 g/L; (5) White blood cell (WBC) count ≥ 1.5 × 10⁹/L, with documented suitable venous access for leukapheresis and no contraindications to leukapheresis; (6) Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without Granulocyte Colony-Stimulating Factor (G-CSF) or other myeloid growth factors within 7 days of screening labs; (7) Absolute lymphocyte count ≥ 0.5 × 10⁹/L; (8) Platelet count ≥ 80 × 10⁹/L without transfusion within 7 days of screening labs; (9) Prothrombin time (PT) prolongation ≤ 4 s above ULN; (10) Oxygen saturation ≥ 95% on room air. 9: Contraception and pregnancy requirements: Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and again before lymphodepleting chemotherapy; must not be breastfeeding. WOCBP and fertile men must use a highly effective contraceptive method from screening until 12 months after CBG131 infusion or study discontinuation, whichever is later.