A Single-arm, Open-label, Dose-escalation/Expansion, Early-phase Clinical Study of Anti-CD70 CAR-T Cell Injection in Patients With CD70-positive Advanced Urological Neoplasms

Changhai Hospital1 site in 1 country60 target enrollmentJuly 31, 2023

ConditionsCD70-positive Advanced Urologic Neoplasms

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: CD70-positive Advanced Urologic Neoplasms
Sponsor: Changhai Hospital
Enrollment: 60
Locations: 1
Primary Endpoint: Adverse Events (AEs)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Detailed Description

This study will include two parts, dose escalation phase (accelerated titration and 3+3 design) followed by a dose expansion phase. All eligible participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by CAR-T cell injection. The dose escalation phase will determine the maximum tolerated dose (MTD) of Anti-CD70 CAR-T cell injection. Additional patients will be enrolled in the dose expansion phase to further characterize the safety profile and evaluate the efficacy of Anti-CD70 CAR-T cell injection, and establish recommended phase 2 dose (RP2D).

Registry

clinicaltrials.gov

Start Date

July 31, 2023

End Date

March 31, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Changhai Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject is≥18 years old (including cut-off value), gender is not limited.
•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.
•At least one measurable lesion according to RECIST v1.
•CD70 should be positive confirmed by Immunohistochemistry/Immunocytochemistry/ Flow Cytometry (IHC/ICC/FCM) in tumor tissue samples.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
•Life expectancy ≥ 3 months.
•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).

Exclusion Criteria

•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.
•Pregnant or lactating women.
•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:
•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.
•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.)
•Patients have received anti-CD70 CAR-T cell therapy.
•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.
•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.
•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.);

Outcomes

Primary Outcomes

Adverse Events (AEs)

Time Frame: 2 years

Incidence and severity of adverse events.

Serious Adverse Events (SAEs)

Time Frame: 2 years

Incidence and severity of serious adverse events.

Adverse Events of Special Interest (AESI)

Time Frame: 2 years

Incidence and severity of adverse event of special interest.

Identification of Maximum Tolerated Dose (MTD)

Time Frame: 4 weeks after the CAR-T cells infusion

Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCL70802 cell injection, at each dose level tested in dose escalation phase.