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This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study, aiming to evaluate the safety and efficacy of CD70-targeted CAR-T cell preparations, and to preliminarily observe the study drug in CD70-positive advanced malignant tumors. The pharmacokinetic characteristics of CAR-T cell preparations for the treatment of patients with CD70-positive advanced malignancies were obtained and the recommended dose and infusion schedule.
According to the different infusion methods, patients will be assigned to three parallel subgroups: intravenous infusion, intrapleural infusion, and intraperitoneal infusion.
Within each subgroup, the study is conducted in two sequential parts:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous of CD70-targeted CAR-T | Experimental | Infusion of CD70-targeted CAR-T cells by dose of 3-10x10^5 cells/kg |
|
| Intrapleural infusion of CD70-targeted CAR-T | Experimental | Infusion of CD70-targeted CAR-T cells by dose of 3-10x10^5 cells/kg |
|
| Intraperitoneal infusion of CD70-targeted CAR-T | Experimental | Infusion of CD70-targeted CAR-T cells by dose of 3-10x10^5 cells/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD70-targeted CAR-T cells | Biological | Administration method: intravenous infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the safety of CAR-T cell preparations in the treatment of CD70-positive advanced malignancies [Safety and Tolerability] | Incidence of adverse events during the study, evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) criteria | 1 month |
| Obtained the recommended dose and infusion regimen of CAR-T cells for the treatment of patients with CD70-positive advanced malignancies [Safety and Tolerability] | Dose-limiting toxicity after CD70 CAR-T cell infusion | 1 month |
| Measure | Description | Time Frame |
|---|---|---|
| Assessing disease control rates of CAR-T cell preparations in CD70-positive advanced malignancies [Effectiveness] | Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria),the minimum value is 0%,maximum value is 100%, and higher scores mean a better outcome. | 1 and 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness] | Objective response rate includes:The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria),the minimum value is 0%,maximum value is 100%, and higher scores mean a better outcome. | 2 years |
Inclusion Criteria:
Age ≥18 years, regardless of gender;
Histologically or cytologically confirmed advanced/metastatic solid tumors (tumors with positive CD70 expression, confirmed histopathological ly with IHC 3+ score);
Failed or intolerant to standard second-line treatments (at least one of the following: tyrosine kinase inhibitors (TKIs), poly(ADP-ribose) polymerase inhibitors (PARPi), anti-angiogenic therapy; disease progression or inability to tolerate surgery, chemotherapy, radiotherapy, or targeted therapy);
At least one measurable lesion per RECIST 1.1 criteria, with measurable lesions defined as:
ECOG performance status of 0-2 ;
Expected survival ≥12 weeks;
No history of severe psychiatric disorders;
Adequate organ function as defined by the following:
Ability to undergo single or venous blood collection, with no contraindications to cellular collection;
Female subjects must agree to use reliable contraception (excluding fertility awareness methods) from the time of informed consent until 1 year after CAR-T cell infusion;
Subject or authorized guardian agrees to participate in the trial and signs the informed consent form (ICF), indicating understanding of the trial's purpose and procedures and willingness to participate.
Exclusion Criteria:
Prior treatment with anti-CD70 therapies;
Active/symptomatic central nervous system (CNS) metastasis or meningeal metastasis: Subjects with treated brain metastases are eligible if treatment was completed ≥4 weeks prior to screening and there is no evidence of progression on imaging;
Prior treatments within specified time frames:
Active infection requiring systemic treatment or uncontrolled infection within 1 week before screening;
History of any other malignancy within the past 3 years, except for treated and stable non-melanoma skin cancer or malignancies treated with curative intent and no evidence of active disease for ≥3 years;
Cardiovascular conditions:
Active or uncontrolled autoimmune diseases such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.;
Positive for HBsAg or HBcAb with elevated HBV DNA in peripheral blood; positive for HCV antibodies with detectable HCV RNA levels; positive for HIV antibodies; positive syphilis test;
Toxicity from prior anti-tumor treatments has not resolved to baseline or ≤grade 1, except for alopecia or peripheral neuropathy;
History of venous thromboembolism (e.g., pulmonary embolism) requiring ongoing anticoagulation treatment, or meeting one of the following criteria:
Pregnant or breastfeeding women;
Other conditions that, in the opinion of the investigator, make the subject unsuitable for participation in the trial.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Donglai Lv, MD | Contact | +8613655600090 | lvxunhuan@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Donglai Lv, MD | The 901 Hospital of Joint Logistics Support Force of People Liberation Army | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The 901 Hospital of Joint Logistics Support Force of People Liberation Army | Recruiting | Hefei | Anhui | 230031 | China |
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| CD70-targeted CAR-T cells | Biological | Administration method: intrapleural infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion. |
|
| CD70-targeted CAR-T cells | Biological | Administration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion. |
|
| To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】 | Cmax: maximum observed level of circulating CAR-T cells in peripheral blood after infusion | From infusion through Month 3 |
| To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】 | To determine the time to maximum observed level of circulating CAR-T cells (Tmax);To estimate AUC0-28d and AUC0-90d for circulating CAR-T cells | From infusion through Month 3 |
| To assess the inflammatory response following CAR-T cell infusion | Serum levels of inflammation-related markers and cytokines, including but not limited to C-reactive protein (CRP), interleukin-6 (IL-6), and ferritin | From infusion through Month 3 |
| Duration of Response (DOR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness] | DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause | 2 years |
| Progress-free survival(PFS) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness] | PFS will be assessed from the first CD70 CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria) | 2 years |
| Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies [Effectiveness] | OS will be assessed from the first CD70 CAR-T cell infusion to death from any cause (Assessed by investigators based on IRECIST criteria) | 2 years |
| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| D008175 | Lung Neoplasms |
| D065646 | Thyroid Carcinoma, Anaplastic |
| D010051 | Ovarian Neoplasms |
| D002583 | Uterine Cervical Neoplasms |
| D013945 | Thymoma |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D005833 | Genital Neoplasms, Female |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D014594 | Uterine Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D018193 | Neoplasms, Complex and Mixed |
| D013953 | Thymus Neoplasms |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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