Trial Title:
MSLN-targeted CAR-T Cells in Solid Tumors.
NCT ID:
NCT05783089
Condition:
Mesothelin-positive Advanced Malignant Solid Tumors
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Anti-mesothelin CAR-T
Anti-MSLN CAR-T
Solid tumor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Accelerated titration and 3+3 design dose escalation phase followed by dose expansion
phase
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Anti-mesothelin CAR-T cells
Description:
Anti-mesothelin CAR-T cells are autologous genetically modified T cells. Cells will be
infused intravenously.
Arm group label:
Anti-mesothelin CAR-T cells Injection
Other name:
UCLM802 Cell Injection
Summary:
This study aims to explore the safety, tolerability and preliminary efficacy of
Anti-Mesothelin CAR-T cells in subjects with Mesothelin-positive advanced malignant solid
tumors.
Detailed description:
This is a single-arm, open-label, exploratory clinical study to evaluate the safety,
tolerability and preliminary efficacy of Anti-Mesothelin CAR-T cells. Patients will be
confirmed to have sufficient expression of mesothelin as part of a prescreening. The
study comprises a dose-escalation component and a dose-expansion component. There are
three cohorts in dose-expansion component. Cohort 1: To explore the effects of different
conditioning chemotherapy regimens on safety, tolerability and efficacy; Cohort 2: To
explore the effects of different administration modes (intravenous injection and local
injection) on safety, tolerability and efficacy; Cohort 3: To explore the effects of
combination immune checkpoint inhibitors on safety, tolerability and efficacy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subject is≥18 years old (including cut-off value), gender is not limited
2. Solid tumors that histological diagnosis of malignancy refractory to, or relapsing
after standard therapy, including but not limited to mesothelioma, pancreatic
cancer, biliary tract cancer, lung cancer, ovarian cancer, gastric cancer, bowel
cancer, thymic carcinoma, esophageal cancer, breast cancer, endometrial cancer.
3. At least one measurable lesion according to RECIST v1.1.
4. Mesothelin should be positive confirmed by Immunohistochemistry/Immunocytochemistry
(IHC/ICC) in tumor tissue samples.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy ≥ 3 months.
7. Adequate function defined as:
Hematological functions: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (Patients
should not receive G-CSF support within 7 days before laboratory examination);
Absolute Lymphocyte Count (ALC) ≥ 0.5 × 109/L; Hemoglobin (HGB) ≥ 80 g/L (Patients
should not be transfused red cells within 7 days before the laboratory examination);
Platelet count (PLT) ≥ 75 × 109/L (Patients should not receive transfusion support
within 7 days before the laboratory examination).
Hepatic functions: Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) ≤ 3.0 × upper limit of normal (ULN); AST and ALT of patients with liver
metastasis ≤ 5 × ULN; Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with
liver metastasis must ≤ 3.0 × ULN; TBIL of patients with Gilbert's Syndrome ≤ 3.0 ×
ULN and Direct bilirubin (DBIL) ≤ 1.5 × ULN.
Coagulation functions: International normalized ratio (INR) ≤ 1.5 × ULN; Activated
partial thromboplastin time (APTT) ≤ 1.5 × ULN (Except for patients who are
receiving therapeutic anticoagulants.).
Renal functions: Serum creatinine (Cr) ≤ 1.5 × ULN; or Creatinine clearance rate
(Ccr) ≥ 60 mL/min.
Cardiac functions: Left ventricular ejection fraction (LVEF) > 45%; Pulmonary
function: Oxygen saturation (SpO2) > 92%.
8. Female participants of childbearing potential must undergo a pregnancy test and the
results must be negative. Female participants of childbearing potential or male
participants whose sex partner has childbearing potential must be willing to use
effective methods of contraception from screening period to at least 1 year after
infusion.
9. Participants must be able to understand the protocol and be willing to enroll the
study, sign the informed consent, and be able to comply with the study and follow-up
procedures.
Exclusion Criteria:
1. Patients have received systemic therapy with cytotoxic chemicals, monoclonal
antibodies, or immunotherapy within 4 weeks or 5 half-lives (which is shorter) prior
to signing informed consent; Patients have received systemic glucocorticoids
(prednisone at a dose of ≥10 mg per day or equivalent) or other immune-suppressive
therapy within 2 weeks prior to signing informed consent; Patients have received
systemic antitumor therapy with a biologic agent or other approved targeted
small-molecule inhibitor within 1 week or five half-lives (which is shorter) prior
to signing informed consent; Patients have received Chinese herbal medicine or
Chinese patent medicine with anti-tumor indication within 1 week prior to signing
informed consent.
2. Pregnant or lactating women.
3. Patients with hepatitis B surface antigen (HBsAg) positive. Patients who is
hepatitis B core antibody (HBcAb) positive and the quantification of HBV DNA in
peripheral blood is higher than the lower limit of detection. Patients who is
hepatitis C virus (HCV) antibody positive and quantification of HCV DNA in
peripheral blood is higher than the lower limit of detection. Patients with human
immunodeficiency virus (HIV) antibody positive, or syphilis antibody positive.
4. The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy,
targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according to
CTCAE, except for hair loss and peripheral sensory nerve disorders.
5. Have received any allogeneic tissue/organ transplantation (including bone marrow
transplantation, stem cell transplantation, liver transplantation, kidney
transplantation), except for the transplantation that does not require
immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
6. Patients have received anti-mesothelin CAR-T cell therapy.
7. Patients who have history of major surgery and unrecovered severe trauma within 4
weeks prior to signing informed consent; or plan to have major surgery within 12
weeks of cell therapy.
8. Presence of known central nervous system metastases, but the following patients will
be allowed: a) Asymptomatic brain metastases; b) Clinically stable (no radiographic
progression within 4 weeks before apheresis and return of any neurologic symptoms to
baseline), and with no need for corticosteroids or other treatment for brain
metastases for ≥ 4 weeks.
9. Patients with clinically significant systemic disease (such as: severe active
infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ
dysfunction) that evaluated by the investigator would impair the patients' ability
to tolerate the treatments used in this study or significantly increase the risk of
complications.
- Uncontrolled severe active infection (sepsis, bacteremia, viremia, etc.);
- Congestive heart failure with New York Heart Association (NYHA) functional
class > 1;
- Clinically significant severe aortic stenosis and symptomatic mitral stenosis;
- Electrocardiogram QTc > 450 msec or QTc > 480 msec in patients with
bundle-branch block;
- Uncontrolled clinically significant arrhythmia within 6 months prior to signing
informed consent;
- Acute coronary syndrome (such as: unstable angina, myocardial infarction)
within 6 months prior to signing informed consent;
- Drug-uncontrolled hypertension (systolic pressure ≥ 160 mmHg and/or diastolic
pressure ≥ 100 mmHg) or pulmonary hypertension;
- Cerebrovascular accident occurred within 6 months prior to signing informed
consent, including transient ischemic attack (TIA), cerebral infarction,
cerebral hemorrhage, subarachnoid hemorrhage;
- A history of active, chronic, or recurrent (within 1 year prior to signing
informed consent) severe autoimmune disease or immune-mediated disease
requiring steroids or other immunosuppressive therapy, including but not
limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis,
inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid
disease, multiple sclerosis. Exceptions: hypothyroidism that can be controlled
only by hormone replacement therapy, skin diseases (such as: vitiligo,
psoriasis) that do not require systemic treatment, coeliac disease that has
been controlled;
- Any form of primary or secondary immunodeficiency, such as severe combined
immunodeficiency (SCID);
- Possibility of bleeding from esophageal or gastric varices evaluated by the
investigator.
10. History of severe systemic hypersensitivity reaction to the drugs/ingredients
[fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO), low molecular dextran,
human serum albumin (HSA), etc.] used in this study.
11. Patients have received attenuated vaccine within 4 weeks prior to signing informed
consent.
12. Patients have received other clinical trials within 4 weeks prior to signing
informed consent.
13. History of another malignancy tumor within the previous five years, except for
adequately treated non-melanoma skin cancer, carcinoma in situ of bladder, stomach,
colon, cervix/dysplasia, melanoma, or breast.
14. History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or evaluated
by investigator, including but not limited to epilepsy, schizophrenia, dementia,
drug and alcohol addictions.
15. For any other reasons, the patients are believed not suitable for participation in
this study by investigators.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
April 2023
Completion date:
April 2027
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Collaborator:
Agency:
UTC Therapeutics Inc.
Agency class:
Industry
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05783089
