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| Name | Class |
|---|---|
| Carbiogene Therapeutics Co. Ltd. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CBG131 CAR-T Cell Injection | Experimental | This Phase I trial follows a conventional 3 + 3 dose-escalation schema. The dose cohorts are designed as follows: (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.The dose escalation rule is as follows: Absence of Dose-Limiting Toxicity (DLT) permits escalation to the next higher cohort; one DLT triggers expansion of the current cohort by three additional subjects at the same dose. If one or more additional DLTs occur during the expansion phase: (1) For the DL1 (starting dose cohort), dose escalation is suspended and de-escalation is considered; (2) For DL2 or higher cohorts, dose escalation stops, and the preceding dose is declared as the Maximum Tolerated Dose (MTD). If no further DLTs occur during expansion, dose escalation proceeds. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CBG131 CAR-T Cell Infusion | Drug | 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 cohort), dose escalation is suspended and de-escalation is considered; (2) in DL2 or higher cohorts, dose escalation stops and the preceding dose is declared the Maximum Tolerated Dose (MTD). If no further DLTs appear, dose escalation proceeds. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and Grading of Adverse Events (AEs) and Serious Adverse Events (SAEs)（Including CRS and ICANS） | This outcome measure assesses the incidence and severity grading of all Adverse Events (AEs) and Serious Adverse Events (SAEs) in subjects. Specifically: a) Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) are graded according to the ASTCT (American Society for Transplantation and Cellular Therapy) consensus criteria; b) All other AEs are graded according to the NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 5.0. Data are collected from leukapheresis enrollment to the end of the follow-up period. | 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 | Dose-Limiting Toxicity (DLT) refers to CBG131-related toxicities (excluding infections and malignancies) occurring within 28 days after CAR-T cell infusion. DLT is determined based on the following criteria: 1) Grade 5 AE; 2) Grade 4 CRS; 3) Grade 4 neurotoxicity; 4) Grade 3 CRS or neurotoxicity that persists for more than 72 hours and fails to improve to ≤Grade 2; 5) Other Grade 4 non-hematologic toxicity that persists for more than 72 hours and fails to improve to ≤Grade 3; 6) Other Grade 3 non-hematologic toxicity that persists for ≥2 weeks; 7) Grade 4 hematologic toxicity that persists for more than 72 hours and fails to improve to ≤Grade 3; 8) Hematologic toxicity of Grade >3 that persists for more than 2 weeks and fails to improve to ≤Grade 2. | Within 28 days after CAR-T cell infusion. |
| Maximum Tolerated Dose (MTD) and Optimal Dosage of CBG131（Determined by 3+3 Dose-Escalation Schema） | This Phase I trial adopts a conventional 3 + 3 dose-escalation schema to determine the Maximum Tolerated Dose (MTD) of CBG131 and further confirm its optimal dosage. The dose cohorts are designed as follows: (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. If no DLT occurs in a cohort, dose escalation proceeds to the next higher cohort; if one DLT occurs, the cohort is expanded by an additional three subjects at the same dose. During the expansion phase: (1) If one or more additional DLTs occur in the DL1 (starting dose cohort), dose escalation is suspended and de-escalation is considered; (2) If one or more additional DLTs occur in DL2 or higher cohorts, dose escalation stops, and the previous dose is declared as the MTD. If no additional DLTs occur during expansion, dose escalation continues. |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor CLDN18.2 Expression Positivity (Assessed by Immunohistochemistry [IHC]) | This outcome measure assesses the positivity of CLDN18.2 expression in primary tumor tissue of subjects. Primary tumor tissue samples obtained within ≤1 year after subject consent must be detected for CLDN18.2 expression by Immunohistochemistry (IHC), and the expression positivity is determined according to the predefined IHC criteria. |
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Inclusion Criteria:
(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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xian Shen | Contact | 13968888872 | shenxian@wmu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Wenzhou Medical University | Wenzhou | Zhejiang | 325000 | China |
De-identified individual participant data, study protocol and metadata will be made publicly available within 6 months after study completion on the ClinicalTrials.gov at https://clinicaltrials.gov.
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|
| Within 28 days after CAR-T cell infusion (DLT assessment period); the MTD is determined after completion of dose escalation for all cohorts. |
| Screening period (before CAR-T cell infusion). |
| Progression-Free Survival (PFS) per RECIST 1.1 Criteria | Progression-Free Survival (PFS) is defined and calculated according to the RECIST (Response Evaluation Criteria in Solid Tumors) Version 1.1 for efficacy evaluation. PFS refers to the interval from the date of CBG131 infusion to the first documented evidence of disease progression or death from any cause, whichever occurs first. Disease progression is determined in accordance with RECIST 1.1 criteria. | 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) | Overall Survival (OS) is defined as the interval from the date of CBG131 infusion to death from any cause. After CAR-T cell infusion, all subjects who discontinue the study for any reason will undergo survival follow-up every 3 months (±2 weeks) until the end of the follow-up period. | 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]） | The Best Overall Response Rate (BORR) is evaluated according to the RECIST 1.1 criteria for antitumor response. Antitumor responses are classified into four categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). BORR is defined as the proportion of subjects who achieve CR or PR during the study period. The number and percentage of subjects achieving CR or PR will be tabulated, and the 95% confidence interval for each percentage will be calculated using the Clopper-Pearson exact method. For the calculation of BORR, each subject's best response recorded at any time during the study will be used. | 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]) | This outcome measure assesses the persistence of CAR-T cells in the peripheral blood of subjects in vivo. Peripheral blood samples are collected at predefined time points, and the number of CAR transgene copies in the samples is detected by quantitative Polymerase Chain Reaction (qPCR) with the unit of copies/μg gDNA. The persistence of CAR-T cells is evaluated based on the dynamic changes of CAR transgene copy number over time. | 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) | This outcome measure assesses the concentration of Interleukin-2 (IL-2) in the serum of subjects. Serum samples are collected at predefined time points, and IL-2 concentration is detected by standard lab cytokine assays. IL-2 is a cytokine involved in immune regulation, and its concentration change reflects the immune response status of subjects after treatment. | 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） | The 3-month Objective Response Rate (ORR) is evaluated according to the RECIST 1.1 criteria. It is defined as the proportion of subjects who achieve Complete Response (CR) or Partial Response (PR) within 3 months after CBG131 infusion. The response status of subjects is determined by tumor assessment according to RECIST 1.1 criteria at the 3-month time point. | Within 3 months (±7 days) after CBG131 infusion. |
| Duration of Response (DOR) per RECIST 1.1 Criteria | Duration of Response (DOR) is defined as the interval from the date of first documented Complete Response (CR) or Partial Response (PR) to the date of first documented evidence of disease progression (assessed by RECIST 1.1 criteria) or death from any cause, whichever occurs first. This outcome measure is only applicable to subjects who achieve an objective response (CR or PR) after CBG131 infusion. | 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 to Response (TTR) is defined as the interval from the date of CBG131 infusion to the date of first documented objective response (including CR and PR) in subjects who achieve an objective response. TTR is described using statistical indicators including mean, median, standard deviation, minimum, and maximum. If no objective response is documented by Week 48 post-infusion, TTR is considered not achieved. | 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 | Duration of Disease Control (DDC) is defined as the interval from the date of first documented Complete Response (CR), Partial Response (PR), or Stable Disease (SD) to the date of first documented Progressive Disease (PD) or death from any cause, whichever occurs first. DDC reflects the duration of disease control in subjects after treatment, and it will be statistically described using mean, median, standard deviation, minimum, and maximum. | 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) | This outcome measure is a post-hoc analysis to explore the correlation between tumor CLDN18.2 expression level (assessed by IHC) and efficacy endpoints (including PFS, OS, ORR, DOR, etc.). Logistic regression and Cox proportional hazards regression models are used for statistical analysis. An exploratory cut-off value of H-score ≥200 is adopted to classify the CLDN18.2 expression level, and the correlation between different expression levels and efficacy endpoints is analyzed. | 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） | This outcome measure assesses the concentration of soluble programmed death-ligand 1 (sPD-L1) in the serum of subjects. Serum samples are collected at predefined time points, and soluble PD-L1 concentration is detected by the central laboratory using standard lab assays. | Screening, Baseline, Week 6, Week 12, Week 18, Week 24, Week 36, Week 48. |
| Serum CA125 Level（Site Lab） | This outcome measure assesses the level of carbohydrate antigen 125 (CA125) in the serum of subjects. Serum samples are collected at predefined time points, and CA125 level is detected by the site laboratory using standard lab assays. CA125 is a tumor marker used for auxiliary assessment of disease status. | Screening, Baseline, Week 6, Week 12, Week 18, Week 24, Week 36, Week 48. |
| Serum Carcinoembryonic Antigen (CEA) Level（Site Lab） | This outcome measure assesses the level of carcinoembryonic antigen (CEA) in the serum of subjects. Serum samples are collected at predefined time points, and CEA level is detected by the site laboratory using standard lab assays. CEA is a tumor marker used for auxiliary assessment of disease status. | Screening, Baseline, Week 6, Week 12, Week 18, Week 24, Week 36, Week 48. |
| Serum Carbohydrate Antigen 19-9 (CA19-9) Level（Site Lab） | This outcome measure assesses the level of carbohydrate antigen 19-9 (CA19-9) in the serum of subjects. Serum samples are collected at predefined time points, and CA19-9 level is detected by the site laboratory using standard lab assays. CA19-9 is a tumor marker used for auxiliary assessment of disease status. | Screening, Baseline, Week 6, Week 12, Week 18, Week 24, Week 36, Week 48. |
| CAR-T Cell Peak Expansion in Vivo (Assessed by Peripheral Blood qPCR for CAR Transgene Copies [copies/μg gDNA]) | This outcome measure assesses the peak expansion level of CAR-T cells in the peripheral blood of subjects in vivo. Peripheral blood samples are collected at predefined time points, and the number of CAR transgene copies in the samples is detected by qPCR with the unit of copies/μg gDNA. The peak expansion level is defined as the maximum value of CAR transgene copy number detected during the follow-up period. | Assessed at Day 1, 4, 7, 11, 15, 21; Week 4, 6, 12, 18, 24, 36, 48; every 6 Months (±2 Months) in Years 2-5; every 12 Months (±2 Months) in Years 5-15; peak expansion determined up to 15 years post-infusion. |
| Area Under the Curve (AUC) of CAR-T Cell Expansion in Vivo (Assessed by Peripheral Blood qPCR for CAR Transgene Copies [copies/μg gDNA]) | This outcome measure assesses the Area Under the Curve (AUC) of CAR-T cell expansion in the peripheral blood of subjects in vivo, which reflects the overall expansion level of CAR-T cells during the follow-up period. Peripheral blood samples are collected at predefined time points, and the number of CAR transgene copies is detected by qPCR. The AUC is calculated based on the dynamic curve of CAR transgene copy number over time, with the unit of copies/μg gDNA × time. | Assessed at Days 1,4,7,11,15,21; Weeks 4,6,12,18,24,36,48; every 6 Months (±2 Months) during Years 2 to 5; every 12 Months (±2 Months) during Years 5 to 15; AUC is calculated based on all detected data up to 15 years post-CBG131 infusion. |
| Serum Interleukin-6 (IL-6) Concentration (Assessed by Lab Cytokine Assay) | This outcome measure assesses the concentration of Interleukin-6 (IL-6) in the serum of subjects. Serum samples are collected at predefined time points, and IL-6 concentration is detected by standard lab cytokine assays. IL-6 is a cytokine closely related to CRS, and its concentration change is used for auxiliary assessment of CRS severity. | Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6. |
| Serum Interferon-γ (IFN-γ) Concentration (Assessed by Lab Cytokine Assay) | This outcome measure assesses the concentration of Interferon-γ (IFN-γ) in the serum of subjects. Serum samples are collected at predefined time points, and IFN-γ concentration is detected by standard lab cytokine assays. IFN-γ is an immune-regulatory cytokine that reflects the anti-tumor immune response of subjects. | Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6. |
| Serum Tumor Necrosis Factor-α (TNF-α) Concentration (Assessed by Lab Cytokine Assay) | This outcome measure assesses the concentration of Tumor Necrosis Factor-α (TNF-α) in the serum of subjects. Serum samples are collected at predefined time points, and TNF-α concentration is detected by standard lab cytokine assays. TNF-α is a pro-inflammatory cytokine involved in the immune response and inflammation regulation after treatment. | Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6. |
| Serum C-X-C Motif Chemokine Ligand 10 (CXCL10) Concentration (Assessed by Lab Cytokine Assay) | This outcome measure assesses the concentration of C-X-C Motif Chemokine Ligand 10 (CXCL10) in the serum of subjects. Serum samples are collected at predefined time points, and CXCL10 concentration is detected by standard lab cytokine assays. CXCL10 is a chemokine involved in immune cell recruitment and anti-tumor immune response. | Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6. |
| Serum Interleukin-8 (IL-8) Concentration (Assessed by Lab Cytokine Assay) | This outcome measure assesses the concentration of Interleukin-8 (IL-8) in the serum of subjects. Serum samples are collected at predefined time points, and IL-8 concentration is detected by standard lab cytokine assays. IL-8 is a pro-inflammatory chemokine involved in neutrophil recruitment and inflammation response after treatment. | Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6. |
| Serum Monocyte Chemoattractant Protein-1 (MCP-1) Concentration (Assessed by Lab Cytokine Assay) | This outcome measure assesses the concentration of Monocyte Chemoattractant Protein-1 (MCP-1) in the serum of subjects. Serum samples are collected at predefined time points, and MCP-1 concentration is detected by standard lab cytokine assays. MCP-1 is a chemokine that mediates monocyte recruitment and participates in immune regulation and inflammation response. | Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6. |
| Serum Interferon-α2 (IFN-α2) Concentration (Assessed by Lab Cytokine Assay) | This outcome measure assesses the concentration of Interferon-α2 (IFN-α2) in the serum of subjects. Serum samples are collected at predefined time points, and IFN-α2 concentration is detected by standard lab cytokine assays. IFN-α2 is an antiviral and immune-regulatory cytokine that participates in the anti-tumor immune response of subjects. | Baseline, Day 0, Day 1, Day 4, Day 7, Day 11, Day 15, Day 21, Week 4, Week 6. |
| Serum TGF-β1 Concentration（Central Lab） | This outcome measure assesses the concentration of transforming growth factor-β1 (TGF-β1) in the serum of subjects. Serum samples are collected at predefined time points, and TGF-β1 concentration is detected by the central laboratory using standard lab assays. | Screening, Baseline, Week 6, Week 12, Week 18, Week 24, Week 36, Week 48. |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
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