Unresectable or Metastatic Clear Cell Renal Cell Carcinoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALCLEAR CAR-T cell injection
CLEAR CAR-T cell injection is an engineered CD70-targeting allogeneic CAR-T cell.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1.Age 18-75 years (inclusive), any gender. 2.Confirmed by histopathology and/or cytology as unresectable or metastatic clear cell renal cell carcinoma; 3.Local progression or metastasis after receiving at least second line therapy \[including at least one immune checkpoint inhibitor (ICI) and at least one vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI)\]; 4.Willing to undergo tumor tissue sample collection or provide previous tumor tissue samples for CD70 expression level testing; 5.Positive CD70 expression by immunohistochemical (IHC) staining of tumor tissue (percentage of positive cells ≥ 10%); 6.At least one measurable lesion according to RECIST v1.1 criteria. 7.Karnofsky Performance Status (KPS) ≥ 70%. 8.Organ function must meet the following criteria: 1. Complete blood count (no G-CSF within 1 week prior to blood count testing. or no pegylated G-CSF within 2 weeks prior to blood count testing): Absolute neutrophil count (ANC) ≥ 1.0×10⁹/L. platelet count (PLT) ≥ 100×10⁹/L. hemoglobin ≥ 80 g/L (excluding bone marrow suppression caused by lymphoma involvement of the bone marrow). 2. Coagulation function: International normalized ratio (INR) ≤ 1.5×ULN, and activated partial thromboplastin time (APTT) ≤ 1.5×ULN. 3. Liver function: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3×ULN (if with liver metastasis, AST and ALT ≤ 5×ULN). total bilirubin ≤ 1.5×ULN. 4. Renal function: Serum creatinine ≤ 1.5×ULN or creatinine clearance (Cockcroft-Gault formula) ≥ 60 mL/min. 5. Cardiac function: Left ventricular ejection fraction (LVEF) on echocardiography (ECHO) ≥ 50%, no pericardial effusion. no clinically significant abnormalities on 12-lead electrocardiogram (ECG). 6. Pulmonary function: End-blood oxygen saturation ≥ 92% while breathing room air without supplemental oxygen. no clinically significant pleural effusion. 9.Subjects and/or their partners of childbearing potential agree to use effective contraceptive measures throughout the entire treatment period and for 52 weeks after treatment, and during this period they must not donate eggs/sperm for assisted reproduction; Female participants of childbearing potential (women who have undergone sterilization surgery or have been postmenopausal for ≥12 months are not considered to have childbearing potential) must present a negative pregnancy test at screening and agree to use effective contraception throughout the study period. 10.Willing to comply with all study procedures and voluntarily participate in this study and sign the informed consent form (ICF). Key
Exclusion criteria
1. Expected survival \< 3 months. 2. Prior or concurrent active malignancy, with the exception of cured or recurrence-free for at least 3 years of cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer, or locally advanced prostate cancer that has received curative treatment, or ductal carcinoma in situ after radical surgery. 3. Prior use of CD70-targeted therapy. 4. Previous treatment with CAR-T or any other genetically engineered cell therapy. 5. History of central nervous system (CNS) disease or clinically significant CNS dysfunction, such as cerebral ischemia/hemorrhage, dementia, cerebellar disease, epilepsy, aphasia, dementia, etc. 6. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation. 7. Occurrence of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina, or other clinically significant cardiac diseases within 12 months prior to screening. 8. Presence of CNS metastasis or symptoms of CNS metastasis. 9. Toxicities from prior therapy have not recovered to CTCAE grade ≤ 1, except for adverse events without safety risks (e.g., alopecia). 10. The anti-tumor therapy received is still within 5 half-lives prior to the planned ET-970 infusion. 11. Presence of uncontrolled active bacterial, fungal, or viral infections, or other infections deemed by the investigator as unsuitable for study participation. 12. Positive for human immunodeficiency virus (HIV) antibody, positive for Treponema pallidum antibody, positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) with detectable peripheral blood HBV DNA, positive for hepatitis C virus (HCV) antibody with detectable HCV RNA; except for infections that can be prevented or controlled with medication as judged by the investigator. 13. History of other autoimmune diseases requiring immunosuppressive therapy. 14. Known severe allergy to the study drug or any of its components. 15. Pregnant or breastfeeding women. 16. Use of any live vaccines against infectious disease within 6 weeks before lymphodepletion conditioning. 17. Participation in another interventional clinical study and receipt of an active investigational drug within 3 months prior to signing the ICF, or intention to participate in another clinical trial or receive treatment for autoimmune diseases outside the protocol during the entire study period. 18. Psychiatric disorders with depression or suicidal tendencies. 19. Presence of any other medical condition that may affect the evaluation of the safety and efficacy of the study drug. 20. Other factors due to which the patient is deemed unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limited toxicity (DLT) | Within 28 days post-infusion | 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) |
| Incidence and severity of AEs and serious adverse events (SAEs) | Within 52 weeks post-infusion | 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. |
| Incidence and severity of AESIs | Within 52 weeks post-infusion | AESI including grade ≥3 Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and GvHD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | Within 52 weeks post-infusion | Including complete response (CR), partial response (PR), or stable disease (SD). |
| Objective Response Rate (ORR) | Within 52 weeks post-infusion | Including complete response (CR), partial response (PR). |
| Duration of Response (DOR) | Within 52 weeks post-infusion | Time from administration to first documented PR or better. |
| Progression-Free Survival (PFS) | Within 52 weeks post-infusion | Time from administration to disease progression or death for any cause, whichever occurs first. |
| Overall Survival (OS) | Within 52 weeks post-infusion | Time from administration to death for any cause. |
| CAR-positive T cells | Within 52 weeks post-infusion | CAR-positive T cells in peripheral blood. |
| CAR gene copy number | Within 52 weeks post-infusion | CAR gene copy number in peripheral blood. |
| Number of CD70 positive cells | Within 52 weeks post-infusion | Number of CD70 positive cells in peripheral blood |
| Change in interleukin-2 (IL-2) levels | Within 52 weeks post-infusion | Peripheral blood IL-2 level changes, with measured in pg/mL. |
| Change in interleukin-6 (IL-6) levels | Within 52 weeks post-infusion | Peripheral blood IL-6 level changes, with measured in pg/mL. |
| Change in interleukin-10 (IL-10) levels | Within 52 weeks post-infusion | Peripheral blood IL-10 level changes, with measured in pg/mL. |
| Change in Tumor Necrosis Factor-α (TNF-α) levels | Within 52 weeks post-infusion | Peripheral blood TNF-α level changes, with measured in pg/mL. |
| Change in Interferon-gamma (IFN-γ) levels | Within 52 weeks post-infusion | Peripheral blood IFN-γ level changes, with measured in pg/mL. |
Countries
China
Outcome results
None listed