Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells for Gastric/Gastroesophageal Junction Adenocarcinoma

NCT06353152 | Recruiting Phase 1

• 1 other identifier: GC506-507
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

A single-arm, open-label early-stage exploratory clinical study to evaluate the safety, tolerability and efficacy of Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells in subjects with gastric/gastroesophageal junction adenocarcinoma.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Occurrence of Dose limiting toxicity.

  Occurrence of DLTs (Dose limiting toxicity).

  Within 28 days after the first infusion

• Incidence of treatment-emergent AEs, AESIs, and SAEs.

  Incidence of treatment-emergent AEs, AESIs, and SAEs.

  48 weeks

Secondary Outcomes (8)

• Disease control rate (DCR)

  12 months

• Objective response rate (ORR)

  12 months

• Duration of disease control (DDC)

  12 months

• Duration of response (DOR)

  12 months

• Progression-free survival (PFS)

  12 months

Study Arms (1)

Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Injection

EXPERIMENTAL

The subjects enrolled will be sequentially assigned to the corresponding dose level.

Drug: Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Injection

Interventions

Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Injection DRUG

single-/multiple-dose infusion

Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-70 years old (including the threshold);
• Subject has pathologically confirmed locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma：Having received at least one standard treatment, with the disease in stable or progressive state, and the subject refusing further treatment or intolerant to existing therapies; Failing second-line treatment;
• Subject's freshly biopsied tumor tissue (if the patient has not received targeted Claudin18.2 therapy, archived tumor tissue within one year is acceptable) has immunohistochemistry confirmed positive expression of Claudin18.2;
• Subject has predicted life expectancy ≥ 90 days;
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Subject is willing to undergo tumor biopsy;
• Subject has at least one measurable tumor lesion on imaging (per RECIST 1.1 criteria);
• Female subjects of childbearing age must not be lactating, and sensitive serum pregnancy test during the screening period must be negative for fertile women. All subjects must use medically accepted contraceptive measures (such as intrauterine devices, contraceptives) throughout the treatment period and 1 year after cell infusion. Male subjects must also avoid sperm donation;
• Subject has adequate organ function reserves: Absolute neutrophil count (ANC) ≥ 1.5×109/L; Absolute lymphocyte count (ALC) ≥ 0.6×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥ 9.0 g/dL; Total bilirubin ≤ 2 × upper limit of normal (ULN) ; ALT and AST ≤ 2.5 × ULN (or ≤ 5 × ULN if bone or liver metastases are present); Creatinine clearance (Cockcroft-Gault method) ≥ 60 mL/min; Stable coagulation function: Prothrombin time (PT) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; Echocardiography shows left ventricular ejection fraction (LVEF) ≥ 55% without moderate or severe pericardial effusion; Baseline oxygen saturation in room air ≥ 92%;
• Subject is able to establish intravenous access, and peripheral blood mononuclear cells can be collected according to the investigator's judgment;
• Subject is willing to sign the informed consent form;
• Subject can communicate well with the investigator, is willing and able to comply with the study plan and will complete the study as per the study requirements.

You may not qualify if:

• Subject has a positive test for Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCV-Ab) or Treponema pallidum antibody (TP-Ab) or Human Immunodeficiency Virus antibody (HIV-Ab). Subjects who are positive for both hepatitis B core antibody (HBcAb) and HBV deoxyribonucleic acid (DNA) will be excluded.
• Subject has other malignant tumors, except for: cured non-melanoma skin cancer, in situ cervical carcinoma, localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ, and other malignant tumors with disease-free survival exceeding 5 years.
• Subject has symptomatic intracranial metastases.
• Subject has central or extensive lung or liver metastases.
• Subject with a maximum target lesion \> 4.0 cm (per RECIST 1.1 criteria).
• The subjects' tumor tissue is positive for HER2 expression.
• Subject has a history of prior anti-tumor treatment or participation in clinical trials: subject has received treatment with CAR-T therapy, or other gene-edited cell therapies; subject has participated in other clinical trials within 28 days before screening; Subject has received local radiotherapy or small molecule chemotherapy within 7 days before leukapheresis, or within at least five half-lives (whichever is longer).; subject has received daily systemic corticosteroid ≥ 15 mg within 7 days before leukapheresis, except inhaled corticosteroids.
• Subject has received vaccination within 28 days before screening.
• Subject has conditions requiring the use of systemic corticosteroids or other immunosuppressive drugs during the study period, as determined by the investigator.
• Subject has acute toxic reactions from previous treatments not recovered to Grade 1 or lower (excluding hematological toxicity, alopecia, and events considered tolerable by the investigator).
• Subject has life-threatening hypersensitivity reactions or other intolerances to cyclophosphamide, fludarabine, or albumin-bound paclitaxel, or severe hypersensitivity to human serum albumin, DMSO, or other substances.
• Subject underwent general anesthesia within 28 days before screening, or has not recovered and clinically stabilized after previous surgical treatment, or is expected to undergo general anesthesia during the study.
• Subject has any unstable cardiovascular diseases within 180 days before screening, including but not limited to unstable angina, myocardial infarction, heart failure (New York Heart Association \[NYHA\] class ≥ III), severe arrhythmias requiring medication, or underwent cardiovascular intervention, coronary artery stenting, or coronary artery bypass grafting within 180 days before screening.
• Subject has a disease or history of central nervous system disorders, such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune diseases involving the CNS.
• Subject has uncontrolled or requiring intravenous treatment for fungal, bacterial, viral, or other infections at the time of screening.

Sponsors & Collaborators

• Peking University: lead
• Gracell Biopharmaceuticals, Inc.: collaborator

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Study Officials

• Lin Shen, PHD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lin Shen, PHD

CONTACT

+86 1088196561; linshenpku@163.com

Changsong Qi, MD

CONTACT

+86 13811394004; xiwangpku@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: April 8, 2024
• Study Start: November 17, 2023
• Primary Completion: November 16, 2025
• Study Completion: November 16, 2025
• Last Updated: April 8, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)