CLEAR CAR-T cell injection (ET-970) is an engineered CD70-targeting allogeneic Chimeric Antigen Receptor T-Cell (CAR-T cell). This is a multi-center, single-arm, open-label, early exploratory clinical study. The objective of this study is to evaluate the safety and preliminary efficacy of ET-970 in unresectable or metastatic clear cell renal cell carcinoma.
ET-970-RCC01 is an open-label study in subjects with ccRCC and will be conducted in two stages: dose-escalation (stage A) and dose-expansion (stage B). The 3+3 dose-escalation design will be adopted in stage A. The aim of stage B is to further assess the safety and efficacy of ET-970 under the dose which has been evaluated as safe in stage A. During treatment period, the subjects will receive a single-dose of ET-970. The duration of participation for each subject will be approximately 57 weeks since the signing of informed consent.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
CLEAR CAR-T cell injection is an engineered CD70-targeting allogeneic CAR-T cell.
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, China
RECRUITINGBiotherapeutic Department of Chinese PLA General Hospital
Beijing, China
RECRUITINGUrology Department of Chinese PLA General Hospital
Beijing, China
RECRUITINGDose limited toxicity (DLT)
DLT is defined as any of the following adverse events (AEs) related to ET-970 occurring within 28 days after ET-970 infusion (CRS and ICANS will be graded according to the ASTCT 2019 criteria, and other AEs will be evaluated using CTCAE v6.0)
Time frame: Within 28 days post-infusion
Incidence and severity of AEs and serious adverse events (SAEs)
AEs refer to any adverse medical events occurring in subjects from the initiation of ET-970 administration during clinical trials. SAEs denote events involving death, life-threatening conditions, significant disability/incapacity, hospitalization or prolonged hospitalization arising after ET-970 administration in subjects.
Time frame: Within 52 weeks post-infusion
Incidence and severity of AESIs
AESI including grade ≥3 Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and GvHD.
Time frame: Within 52 weeks post-infusion
Disease control rate (DCR)
Including complete response (CR), partial response (PR), or stable disease (SD).
Time frame: Within 52 weeks post-infusion
Objective Response Rate (ORR)
Including complete response (CR), partial response (PR).
Time frame: Within 52 weeks post-infusion
Duration of Response (DOR)
Time from administration to first documented PR or better.
Time frame: Within 52 weeks post-infusion
Progression-Free Survival (PFS)
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Time from administration to disease progression or death for any cause, whichever occurs first.
Time frame: Within 52 weeks post-infusion
Overall Survival (OS)
Time from administration to death for any cause.
Time frame: Within 52 weeks post-infusion
CAR-positive T cells
CAR-positive T cells in peripheral blood.
Time frame: Within 52 weeks post-infusion
CAR gene copy number
CAR gene copy number in peripheral blood.
Time frame: Within 52 weeks post-infusion
Number of CD70 positive cells
Number of CD70 positive cells in peripheral blood
Time frame: Within 52 weeks post-infusion
Change in interleukin-2 (IL-2) levels
Peripheral blood IL-2 level changes, with measured in pg/mL.
Time frame: Within 52 weeks post-infusion
Change in interleukin-6 (IL-6) levels
Peripheral blood IL-6 level changes, with measured in pg/mL.
Time frame: Within 52 weeks post-infusion
Change in interleukin-10 (IL-10) levels
Peripheral blood IL-10 level changes, with measured in pg/mL.
Time frame: Within 52 weeks post-infusion
Change in Tumor Necrosis Factor-α (TNF-α) levels
Peripheral blood TNF-α level changes, with measured in pg/mL.
Time frame: Within 52 weeks post-infusion
Change in Interferon-gamma (IFN-γ) levels
Peripheral blood IFN-γ level changes, with measured in pg/mL.
Time frame: Within 52 weeks post-infusion