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

Overview

The goal of this clinical trial is to learn if CBG131 works to treat advanced gastric cancer or pancreatic cancer in adults whose tumors are CLDN18.2-positive. It will also learn about the safety of CBG131 and find the best dose to use. The main questions it aims to answer are: Is CBG131 safe, and what medical problems do participants have when receiving it? Does CBG131 shrink tumors in participants with CLDN18.2-positive cancers? How long do the CAR-T cells stay and work in the body? Researchers will test different doses of CBG131 to see which dose is safest and most effective. This is an early-stage trial, so there is no placebo group-everyone who joins will receive the actual treatment. Participants will: Have their blood cells collected through a procedure called leukapheresis (so the CAR-T cells can be made). Receive chemotherapy for 3 days to prepare their body for the CAR-T cells Get a single infusion of CBG131 CAR-T cells through an IV. Visit the clinic frequently for the first month, then regularly for 2 years for checkups, blood tests, and tumor assessments. Keep track of their symptoms and any side effects they experience.

Interventions

• Drug CBG131 CAR-T Cell Infusion
  This Phase I trial follows a conventional 3 + 3 dose-escalation schema. Cohorts: (1) DL1 (de-escalation cohort): 0.5×10⁸ CAR⁺ T cells; (2) DL1 (starting dose cohort): 1×10⁸ CAR⁺ T cells; (3) DL2: 2×10⁸ CAR⁺ T cells. Three subjects are enrolled in each cohort. Absence of Dose-Limiting Toxicity (DLT) permits dose escalation; one DLT triggers expansion of the cohort by three additional subjects at the same dose. If, during expansion, one or more additional DLTs occur: (1) in the DL1 (starting dose

Primary outcome measures

• Incidence and Grading of Adverse Events (AEs) and Serious Adverse Events (SAEs)（Including CRS and ICANS） [Time frame: From leukapheresis enrollment up to 15 years post-CBG131 infusion, or until study withdrawal, loss to follow-up, or death of the subject, whichever comes first.]
• Incidence and Determination of Dose-Limiting Toxicity (DLT) Related to CBG131 [Time frame: Within 28 days after CAR-T cell infusion.]
• Maximum Tolerated Dose (MTD) and Optimal Dosage of CBG131（Determined by 3+3 Dose-Escalation Schema） [Time frame: Within 28 days after CAR-T cell infusion (DLT assessment period); the MTD is determined after completion of dose escalation for all cohorts.]

Secondary outcome measures (12)

• Tumor CLDN18.2 Expression Positivity (Assessed by Immunohistochemistry [IHC]) [Time frame: Screening period (before CAR-T cell infusion).]
• Progression-Free Survival (PFS) per RECIST 1.1 Criteria [Time frame: From the date of CBG131 infusion to the first documented evidence of disease progression or death from any cause, whichever occurs first; assessed up to Week 48 (±7 days), with interim assessments at Weeks 6, 12, 18, 24, 36 and 48 (±7 days).]
• Overall Survival (OS) [Time frame: From the date of CBG131 infusion to death from any cause, whichever occurs first; assessed up to 2 years post-treatment (or until loss to follow-up, withdrawal of consent, or death, whichever comes first), with follow-up every 3 months (±2 weeks).]
• Best Overall Response Rate (BORR) per RECIST 1.1 Criteria（Proportion of Subjects Achieving Complete Response [CR] or Partial Response [PR]） [Time frame: Weeks 6, 12, 18, 24, 36 and 48 (±7 days); the best overall response of each subject is determined based on the responses recorded at all above time points.]
• CAR-T Cell Persistence in Vivo (Assessed by Peripheral Blood qPCR for CAR Transgene Copies [copies/μg gDNA]) [Time frame: Assessed at Day 1, Day 4, Day 7, Day 11, Day 15, Day 21;Week 4, Week 6, Week 12, Week 18, Week 24, Week 36, Week 48;every 6 Months(±2 Months) during Years 2 to 5;every 12 Months(±2 Months) during Years 5 to 15;assessed up to 15 years post-CBG131 infusion]
• Serum Interleukin-2 (IL-2) Concentration (Assessed by Lab Cytokine Assay) [Time frame: Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6.]
• 3-month Objective Response Rate (ORR) per RECIST 1.1 Criteria（Proportion of Subjects Achieving CR or PR） [Time frame: Within 3 months (±7 days) after CBG131 infusion.]
• Duration of Response (DOR) per RECIST 1.1 Criteria [Time frame: From the date of first documented CR or PR to the date of first documented disease progression (per RECIST 1.1 criteria) or death from any cause, whichever occurs first; assessed up to 15 years post-CBG131 infusion.]
• Time to Response (TTR) per RECIST 1.1 Criteria [Time frame: From the date of CBG131 infusion to the first documented CR or PR; assessed up to Week 48 (±7 days) (if no response is documented by Week 48, TTR is considered not achieved).]
• Duration of Disease Control (DDC) per RECIST 1.1 Criteria [Time frame: From the date of first documented CR, PR, or SD (per RECIST 1.1 criteria) to the date of first documented PD or death from any cause, whichever occurs first; assessed up to 15 years post-CBG131 infusion.]
• Correlation Between Tumor CLDN18.2 Expression Level (Assessed by IHC) and Efficacy Endpoints (Post-hoc Analysis) [Time frame: Post-hoc correlation analysis between tumor CLDN18.2 level and efficacy endpoints; analysis will be performed after completion of efficacy follow-up (assessed up to 15 years post-CBG131 infusion).]
• Serum Soluble PD-L1 Concentration（Central Lab） [Time frame: Screening, Baseline, Week 6, Week 12, Week 18, Week 24, Week 36, Week 48.]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• Pregnant or lactating women.
• 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.
• 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.
• 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).
• 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.
• History of organ transplantation or on transplant waiting list.
• 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.
• 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.
• Requirement for warfarin or heparin anticoagulation.
• Chronic antiplatelet therapy at doses exceeding aspirin 100 mg/day or clopidogrel 75 mg/day.
• Toxicities from prior therapies not resolved to ≤ Grade 1 or baseline (except alopecia, pigmentation, or laboratory abnormalities allowed by protocol) at informed-consent signature.
• 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).
• Clinically relevant thyroid dysfunction (TT4, TT3, FT3, FT4, TSH outside normal limits per investigator).
• Active autoimmune disease (e.g. psoriasis, RA) or any condition requiring chronic immunosuppressive therapy.
• Known or suspected CNS metastases.
• Single target lesion > 4 cm in longest diameter (or > 4 cm short axis for lymph nodes) before leukapheresis.
• Symptomatic ascites or ascites requiring repeated paracentesis or intraperitoneal therapy; small-volume radiologic ascites permitted if asymptomatic.
• Any other condition that, in the opinion of the investigator, renders the subject unsuitable for participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Identifiers

NCT: NCT07394205 · TXB2025 No. (005)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗