Overview

This is a single-arm, open-label, exploratory clinical study to evaluate the safety, tolerability and preliminary efficacy of Anti-CD70 CAR-T cell injection in patients with CD70-positive Advanced Urologic Neoplasms.

Eligibility

Inclusion Criteria:

• 1. Subject is≥18 years old (including cut-off value), gender is not limited. 2. Histopathologically confirmed tumors of the urinary system (including renal cancers and urothelial cancers). Renal cancers should have failed after targeted therapy and/or immunotherapy. Urothelial cancers should have failed after chemotherapy and/or immunotherapy. Or subjects are unable to tolerate or lack effective therapies. 3. At least one measurable lesion according to RECIST v1.1. 4. CD70 should be positive confirmed by Immunohistochemistry/Immunocytochemistry/ Flow Cytometry (IHC/ICC/FCM) 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 Estimated glomerular filtration rate
        (eGFR) ≥30ml/(min·1.73 m2)(Calculated by CKD⁃EPI).
        Cardiac functions: Left ventricular ejection fraction (LVEF) > 50%; 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.
             Patients with syphilis antibody positive and tolulized red unheated serum test (TRUST)
             titer ≥ 1:4.
             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-CD70 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; 10. Any form of
                  primary or secondary immunodeficiency, such as severe combined immunodeficiency
                  (SCID); 11. 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.
                  12. Patients have received attenuated vaccine within 4 weeks prior to signing
                  informed consent.
                  13. Patients have received other clinical trials within 4 weeks prior to signing
                  informed consent.
                  14. 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.
                  15. 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.
                  16. For any other reasons, the patients are believed not suitable for
                  participation in this study by investigators.