Overview

Study of αPD1-MSLN-CAR T Cells to Evaluate the Safety, Tolerability, and Effectiveness for Patients With MSLN-positive Advanced Solid Tumors

Status:
Not yet recruiting
Trial end date:
2023-10-30
Target enrollment:
0
Participant gender:
All
Summary
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies (αPD1-MSLN-CAR T cells) in patients with solid tumors.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Shanghai Cell Therapy Group Co.,Ltd
Criteria
Inclusion Criteria:

- Patients must have a histological or cytological diagnosis of advanced solid tumors,
such as ovarian cancer,Cholangiocarcinoma,colorectal cancer;

- Patients must have failed established standard medical anti-cancer therapies;

- 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;

- Subjects must meet blood coagulation parameters and have adequate venous peripheral
access for apheresis. Patients must also have adequate mononuclear cells for CAR T
cell manufacturing;

- Staining of MSLN must be greater than 50% of the cells in the tumor tissue and with
apparent expression in the membrane. PD-L1 expression must be positive. Tissue
obtained for the biopsy must be ≤1 year prior to enrollment for screening, not have
been previously irradiated or exposed to chemotherapy. If unavailable, new tissue
material from a recently obtained surgical or diagnostic biopsy is mandatory for this
trial;

- Satisfactory organ and bone marrow function as defined by the following:

1. Adequate bone marrow function in the opinion of the Investigator for
lymphocyte-depleting chemotherapy: 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 (≤2.5x if there is hepatic metastasis);

3. Creatinine must be less than or equal to one and one half times (≤ 1.5x) the
institutional normal upper limit or eGFR ≥ 60ml/min/1.73m^2
[eGFR=186×(age)-0.203×SCr-1.154(mg/dl),for female the eGFR shoud be timed by
0.742];

4. International normalized ratio (INR) or the PT is not greater than one and one
half times (≤ 1.5) the upper limit of normal;

5. Lung function: ≤ CTCAE grade 1 dyspnea and SaO2≥ 91%

6. 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;

- For concurrent medication:

1. Systemic therapeutic corticosteroids must be stopped 72 hours before CAR-T
infusion. However, patients using physiologic replacement doses of
corticosteroids, or its equivalent, will be considered eligible;

2. Immunosuppressive therapy must be stopped within four (4) weeks prior to
enrollment;

- 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:

- Prior therapy with targeted therapy or cell therapy against MSLN;

- Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell
therapy home and abroad;

- Active bacteria, viral or fungal infection, and not contained after anti-infective
therapy (positive results in the blood ≤72 hours before infusion);

- Patient is positive for Syphilis, Human Immunodeficiency Virus (HIV) , active
Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected);

- Patient has a medical condition such as autoimmune disease or organ transplantation
that requires chronic systemic steroid therapy or requires any other form of
immunosuppressive medication;

- 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;

- Patient has a history or current evidence of any condition such as neurotic,
psychiatric, immune, metabolic and infectious disease, on any therapy, or laboratory
abnormality that might confound the results of the study, interfere with the patient's
participation for the full duration of the study, or is not in the best interest of
the patient to participate, in the opinion of the treating Investigator;

- Patient has a known history of a hematologic malignancy, or of another malignant
primary solid tumor concurrently, with the exception of :

1. Patients with in situ cervical cancer or breast cancer with no evidence of
disease for ≥ 3 years after curative treatments;

2. Patients who underwent successful definitive resection of in situ cancer with no
evidence of disease for ≥5 years;

- Has had chemotherapy, radioactive, small molecules, biological cancer therapy,
immunotherapy or other investigational drugs within 4 weeks prior to the initiation of
the study;

- Pregnant or breastfeeding women;

- Investigators think that patient has a history or current evidence of any condition,
therapy, or laboratory abnormality that might confound the results of the study,
interfere with the patient's participation for the full duration of the study and
cooperation with the requirements of the trial, uncontrolled medical, psychological,
familial, sociological, or geographical conditions, or is not in the best interest of
the patient to participate.