Treatment of advanced solid tumors using fast CAR T cells

An Exploratory Study on the Treatment of Advanced Solid Tumors by Secretory PD1 Nanoantibody Targeting Mesothelin Fast CAR T Cells

This study is testing a new type of CAR T cell therapy to see if it can help people with advanced solid tumors who haven't had success with other treatments.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai Cell Therapy Group Co.,Ltd (industry)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy, radiation, chimeric antigen receptor
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06249256 on ClinicalTrials.gov

What this trial studies

This exploratory clinical study evaluates the safety and tolerability of fast autologous mesothelin-targeted chimeric antigen receptor T cells that secrete PD-1 nanobodies in patients with advanced solid tumors. It involves a single-arm, open-label, dose escalation approach to assess the efficacy of the treatment. The study includes a screening phase, apheresis, lymphodepletion, and post-infusion assessments to monitor patient responses and safety. The main goal is to determine the effectiveness of the BZT2312 treatment in patients who have not responded to standard therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with advanced solid tumors expressing mesothelin and PD-L1, who have failed standard treatments.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have limited treatment alternatives.

How similar studies have performed: Other studies using CAR T cell therapies have shown promising results, indicating potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

* Patients diagnosed with advanced solid tumors through histopathological diagnosis have a positive rate of ≥ 50% for mesothelin expression membrane in tumor tissue samples, PD-L1 positive expression, and sample sources within 2 years；
* Late stage malignant solid tumor patients who have failed standard treatment or are intolerant to such treatment and do not have a standard effective treatment plan；
* Greater than or equal to 18 years of age and less than or equal to 70 years of age on day of signing informed consent；
* Life expectancy \>3 months；
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；
* Satisfactory organ and bone marrow function as defined by the following:

  1. absolute neutrophil count must be greater than ≥ 1.5×109/L, lymphocyte count must be greater than ≥ 0.5×109/L, platelets must be greater than ≥ 90×109/L, hemoglobin must be greater than ≥ 90g/L without transfusion within 7 days or dependency on EPO;
  2. Total bilirubin must be less than or equal to two times (≤2.0x) the institutional normal upper limit; transaminases, serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), must be less than or equal to 2.5 times (≤2.5x) the institutional normal upper limit (≤5x if there is hepatic metastasis);
  3. International normalized ratio (INR) or the PT is not greater than one and one half times (≤ 1.5) the upper limit of normal;
  4. Lung function: ≤ CTCAE grade 1 dyspnea and SaO2≥ 91%
  5. Cardiac function: cardiac ejection fraction (LVEF) must be greater than fifty percent (≥50%) by echocardiogram or MUGA one month before enrollment.
* Subjects must have measureable disease as defined by RECIST 1.1 criteria;
* Subjects sufficiently understand the trial and willingly sign the informed consent；
* Male and Female subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for at least 12 months following the last dose of the study cell infusion and until no CAR-T cells can be detected after two consecutive PCR tests.

Exclusion Criteria:

* Subjects who have undergone other anti-tumor treatments (including radiation therapy, chemotherapy, small molecule, biological or immunotherapy, and other study drugs) other than lymphocytes depletion allowed by the protocol within one month prior to CAR-T infusion;
* Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell therapy home and abroad;
* Pregnant or breastfeeding women;
* Positive serological reactions for HIV and syphilis; Hepatitis B surface antigen positive, hepatitis B core antibody positive, and hepatitis B virus DNA copy number higher than the detection limit and/or greater than or equal to 1000 copies/mL; Or Hepatitis C virus infected individuals;
* Any uncontrollable active infection, coagulation disorders, or any other major illness;
* Patients with autoimmune diseases, organ transplantation and other immune related diseases under treatment, or long-term use of immunosuppressive drugs such as glucocorticoids: a. Glucocorticoids: users cannot stop using CAR-T cells 72 hours before infusion; b. Immunosuppressants other than glucocorticoids cannot be stopped ≥ 4 weeks before enrollment;
* Patients who are allergic to BZT2312 components;
* History of severe cardiac or pulmonary disease, including hypertension that cannot be controlled by medication, and any of the conditions occurred within the past 6 months: congestive heart failure (New York Heart Association functional classification ≥3), cardiac angioplasty and stents, myocardial infarction, unstable angina, or other clinically significant heart disease;
* Detectable clinically relevant central nervous system (CNS) metastases and/or pathology such as epilepsy/seizure, brain Ischemia/ hemorrhage, dementia, cerebellar disease, or autoimmune disease affecting central nervous system
* Patients at high risk of causing bleeding or perforation;
* Patients who had undergone major surgical procedures or significant trauma within 4 weeks before apheresis, or who were expected to require major surgery during the study period;
* Patient has a known history of a hematologic malignancy, or of another malignant primary solid tumor concurrently, with the exception of :Patients with in situ cervical cancer or breast cancer with no evidence of disease for ≥ 3 years after curative treatments;Patients who underwent successful definitive resection of in situ cancer with no evidence of disease for ≥5 years;
* Other circumstances that were deemed by the investigator to be inappropriate for trial participation.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Mengchao Cancer Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Jinxing Lou — Shanghai Mengchao Cancer Hospital
• Study coordinator: Yong Xia

Conditions: Solid Tumor