Solid Tumor, Adult Clinical Trial
Official title:
Phase I/II Study of CD70 Targeted CAR-T Cell Treatment in CD70 Positive Advanced/Metastatic Solid Tumors
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).
Status | Recruiting |
Enrollment | 30 |
Est. completion date | December 31, 2026 |
Est. primary completion date | December 31, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion Criteria: 1. Age 18-75 (inclusive). 2. ECOG performance status =2 and Estimated life expectancy of more than 3 months. 3. Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. CD70 antigen expression level = 30%. 4. At least one measurable lesion at baseline per RECIST version 1.1. 5. Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor rebiopsy in the process of this study. 6. Adequate organ function as defined by the following criteria: ANC=1.5x10^9/L; Platelet count =75x10^9/L; Hemoglobin =90 g/L;Serum AST and serum ALT, =3.0 x ULN (=5 x ULN for patients with liver cancer or metastases); Total serum bilirubin =1.5 x ULN(=3 x ULN for patients with liver cancer or metastases); Serum creatinine =1.5 xULN or creatinine clearance of =60 mL/min. 7. Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year. 8. Ability to understand and sign a written informed consent documen. Exclusion Criteria: 1. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. 2. Received cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives before enrollment; 3. Pregnant, lactating, or breastfeeding females; 4. Known positive test result for human immunodeficiency virus (HIV) oracquired immune deficiency syndrome (AIDS);Active infection of hepatitis B virus (HBV), or hepatitis C virus (HCV); 5. History of allergy or intolerance to study drug components; 6. Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation; 7. Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered. 8. Known brain metastases or active central nervous system (CNS).Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening. 9. Previous or concurrent cancer within 5 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors; 10. Any serious underlying medical (eg, pulmonary, renal, hepatic,gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements; 11. Vaccination within 30 days of study enrollment; 12. Previously received CD70-CAR T cell therapy; 13. Being participating any other trials or withdraw within 4 weeks; 14. Researchers believe that other reasons are not suitable for clinical trials. |
Country | Name | City | State |
---|---|---|---|
China | China | Beijing | Iotherapeutic Department Of Chinsese PLA Gereral Hospital |
Lead Sponsor | Collaborator |
---|---|
Chinese PLA General Hospital | UTC Therapeutics Inc. |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | |
Primary | 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 | |
Primary | 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 | |
Secondary | 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 | |
Secondary | Objective response rate (ORR) | Objective response rate includes complete response and partial response defined by investigators according to RECIST 1.1or iRECIST criteria. | Up to 3 years | |
Secondary | 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 | |
Secondary | 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 | |
Secondary | 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 | |
Secondary | 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 | |
Secondary | Pharmacodynamics: Peak level of cytokines in serum | The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-a (TNF-a), 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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT04551885 -
FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors
|
Phase 1 | |
Completed |
NCT05054348 -
First-in-human Study of IO-108 as Single Agent and in Combination With a PD-1 Immune Check Point Inhibitor in Patients With Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT04474470 -
A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT06088004 -
Phase Ⅰ/Ⅱ Clinical Study to Evaluate ABO2011 Monotherapy in Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT05055609 -
Open-Label, Dose-Escalation With Expansion to Assess the Safety, Tolerability, and PK of TRE-515 in Subjects With Solid Tumors
|
Phase 1 | |
Completed |
NCT04020185 -
Safety and Efficacy Study of IMSA101 in Refractory Malignancies
|
Phase 1/Phase 2 | |
Withdrawn |
NCT05071846 -
MVX-ONCO-2 in Advanced Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05607199 -
A First in Human Study of AUR 103 Calcium to Evaluate Safety, Pharmacokinetics and Pharmacodynamics
|
Phase 1 | |
Active, not recruiting |
NCT04552288 -
Study of Benralizumab in People With Skin Side Effects Caused by Cancer Therapies
|
Phase 2 | |
Active, not recruiting |
NCT06026254 -
A Rollover Study for Subjects Who Completed Participation in IMSA101-101 Trial
|
Phase 1 | |
Recruiting |
NCT06144671 -
GT201 Injection For The Treatment Of Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT06032845 -
Cryoablation Combined With Tislelizumab Plus Lenvatinib In Previously Treated Solid Tumors (CASTLE-11)
|
Phase 2 | |
Not yet recruiting |
NCT06398418 -
R-5780-01 In Combination With PD-1 Checkpoint Inhibitors (Checkpoint Protein on Immune Cells Called T Cells) in Patients With Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05276284 -
Thiopurine Enhanced Mutations for PD-1/Ligand-1 Efficacy
|
Phase 1/Phase 2 | |
Recruiting |
NCT04121442 -
Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04221204 -
A Monotherapy in Subjects With Advanced Solid Tumors
|
Phase 1 | |
Terminated |
NCT03992326 -
Adoptive Transfer Of Autologous Tumor-Infiltrating Lymphocytes in Solid Tumors
|
Phase 1 | |
Terminated |
NCT05435339 -
A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy
|
Phase 1/Phase 2 | |
Recruiting |
NCT04981119 -
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing
|
||
Recruiting |
NCT06075849 -
Phase I Study to Evaluate Safety and Anti-tumor Activity of PB101, an Anti-angiogenic Immunomodulating Agent
|
Phase 1 |