NCT04976218

TGFβR-KO CAR-EGFR T Cells in Previously Treated Advanced EGFR-positive Solid Tumors

Phase Ⅰ Study of EGFR Targeted TGFβR-KO CAR T Cells in the Treatment of Previously Treated Advanced EGFR-positive Solid Tumors

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. However, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME. In this study, we construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in previously treated advanced EGFR positive solid tumors.

Detailed description

Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. Different from the promising efficacy in leukemia, lymphoma and multiple myeloma, however, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME, which plays a key role in promoting tumor initiation, metastasis, and suppressing anti-tumor immunity. In this phase Ⅰstudy, we plan to construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in the treatment of previously treated advanced EGFR antigen overexpressing solid tumors.

Conditions

• Solid Tumor, Adult
• EGFR Overexpression

Interventions

Type	Name	Description
BIOLOGICAL	TGFβR-KO CAR-EGFR T Cells	Enrolled patients will be administered TGFβR-KO CAR-EGFR T Cells in 3+3 based escalation manner. The infused CAR+ T cell dose in phase IA will be started initially at 1-2×10\^5/kg, dose 2 will be 1×10\^6/kg，and dose 3 will be 1×10\^7/kg, if DLT occurs in dose level 3, the following dose will return to 5×10\^6/kg. In expansion period, the dose of infused CAR+ T cells will be determined by the recommended cell dose from phase IA.

Timeline

• Start date: 2022-03-15
• Primary completion: 2023-12-20
• Completion: 2024-12-31
• First posted: 2021-07-26
• Last updated: 2022-11-16

Locations

1 site across 1 country: China