Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| UTC Therapeutics Inc. | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
In this single-center, single-arm,prospective, open-label, phase 1/2 study, the safety and efficacy of autologous CD70 targeted chimeric antigen receptor modified T (CAR-T) cell therapy will be evaluated in patients with CD70 antigen positive advanced/metastatic solid tumors . In this clinical trial, at least 12 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD70-CAR cell therapy according to the "3+3" principle. In dose expansion period, additional at most 21 eligible patients will be enrolled to receive CD70-CAR-T cell therapy at dose of recommended phase 2 dose(RP2D).
Currently, CAR-T cell therapy has already achieved tremendous success in the treatment of hematological malignancies,however, it remains a severe challenge to treat solid tumors due to multiple obstacles,such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity.
CD70 is a member of the tumor factor superfamily and has been found to be highly expressed on the surface of several solid and hematological tumors, correlating with inferior prognosis.Targeting CD70 has emerged as potential novel immunotherapeutic strategy. Investigators have developed CD70-CAR-T cells that could effectively expand and survive,producing strong anti-tumor effects in animal models. Based on the preclinical data, we conduct this clinical trial in order to test the the safety profiles and anti-tumor activities of CD70-CAR-T cells in vivo. In dose escalation period, at least 12 eligible patients will be enrolled and receive 3 doses of CD70-CAR-T cell therapy (1 × 10^6 cells/kg, 3 × 10^6 cells/kg, 1 × 10^7 cells/kg) according to the "3+3" principle. In dose expansion period, additional at most 21 eligible patients will be enrolled to receive CD70-CAR-T cell infusion at dose of RP2D, which is determined by data from dose escalation period, including occurrence of dose limiting toxicities (DLT), pharmacokinetics/pharmacodynamics, efficacy and other parameters, to furtherly evaluate the safety and efficacy profiles of CD70-CAR-T cell therapy.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CD70-targeting CAR-T cells | Experimental | Enrolled participants will be given a preconditioning regimen consisted of albumin-bound paclitaxel, cyclophosphamide and fludarabine before the infusion of CD70-CAR-T cells. Enrolled patients in this arm will be administered CD70-CAR-T cells in 3+3 based escalation manner. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD70-targeting CAR-T cells | Biological | Dose escalation: Dose1 (1×10^6 cells/kg) , Dose 2(3×10^6 cells/kg) ,Dose 3 (1×10^7cells/kg); Dose expansion: RP2D Drug: Albumin-bound paclitaxel Administered intravenously at dose of 100-200mg/m2 on day -5; Drug: Cyclophosphamide Administered intravenously at dose of 15-30mg/kg on day -3 and day -2; Drug: Fludarabine Administered intravenously at dose of 30mg/m2 on day -3 and day -2; |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment related adverse events | AE is defined as any adverse medical event from the date of randomization to 12 months after CD70-CAR-T cell infusion. Among them, CRS and ICANS were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0. | Up to 12 months since the initiation of CD70-CAR-T cell therapy. |
| Incidence of dose limiting toxicities (DLTs) | DLT was defined as CD70-CAR-T cells-related events with onset within first 28 days following infusion: The development of Grade (G) 3 or higher grade CRS lasting > 2 weeks; All G4 non-hematologic toxicities. | Up to 28 days since the initiation of CD70-CAR-T cell therapy |
| Maximum tolerated dose (MTD) | MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined. | Up to 28 days since the initiation of CD70-CAR-T cell therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Number and copy number of CD70-CAR-T cells | Number and copy number of CD70-CAR-T cells are evaluated by number in peripheral blood and tumor tissue. | Up to 3 years |
| Objective response rate (ORR) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weidong Han, Ph.D | Contact | 010-66937231 | +86 | hanwdrsw@sina.com |
| Yang Liu, M.D | Contact | : 010-66939460 | +86 | liuyang301blood@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Yangbin Zhao, Ph.D | UTC Therapeutics Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| China | Recruiting | Beijing | Iotherapeutic Department of Chinsese PLA Gereral Hospital | China |
Not provided
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
Objective response rate includes complete response and partial response defined by investigators according to RECIST 1.1or iRECIST criteria.
| Up to 3 years |
| Progression Free Survival (PFS) | Progression Free Survival is defined as the time from the initiation of CD70-CAR-T cell therapy to documented disease progression or death. | Up to 3 years |
| Time to response (TTR) | Time to response is defined as the time from the initiation of CD70-CAR-T cell therapy to first assessed CR or PR by investigators according to RECIST 1.1or iRECIST criteria. | Up to 3 years |
| Duration of response (DOR) | Duration of response is defined as the time from objective response until documented tumor progression among responders. | Up to 3 years |
| Overall Survival (OS) | Overall Survival is defined as the time from the initiation of CD70-CAR-T cell therapy to documented disease progression or death. | Up to 3 years |
| Pharmacodynamics: Peak level of cytokines in serum | The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C reactive protein (CRP), ferritin. Peak was defined as the maximum post-baseline level of the cytokine. | Up to 28 days since the initiation of CD70-CAR-T cell therapy |