NCT06939270

CD73/AXL Targeted HypoSti.CAR-T Cells in CD73/AXL Positive Advanced/Metastatic Solid Tumors

Phase I/II Clinical Trial of CD73/AXL Targeted HypoSti.CAR-T Cells in Treating Patients With CD73/AXL Positive Advanced/Metastatic Solid Tumors

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• 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

In this single-center, single-arm,prospective, open-label, phase 1/2 study, the safety and efficacy of novel autologous hypoxia-activated CAR-T cell therapy targeting CD73 and AXL ( CD73/AXL.HypoSti.CAR-T) will be evaluated in patients with CD73/AXL 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 CD73/AXL.HypoSti.CAR-T cell therapy according to the "3+3" principle. In dose expansion period, additional at most 21 eligible patients will be enrolled to receive CD73/AXL.HypoSti.CAR-T cell therapy at dose of recommended phase 2 dose(RP2D).

Detailed description

Currently, CAR T-cell therapy still faces significant challenges in its application to solid tumors due to multiple obstacles, including the lack of tumor-specific antigens, the complex immunosuppressive tumor microenvironment (TME), tumor heterogeneity, and on targeted/non-targeted (OTOT) toxicity. Previous studies have found that intratumoral hypoxic microenvironment facilitated the development and metastasis of tumor cells. Meanwhile, cytotoxic T cells, including CAR-T cells, struggle to survive and proliferate in this low-oxygen microenvironment. CD73 (also known as 5'-nucleotidase) and AXL (a receptor tyrosine kinase) are both overexpressed in multiple solid tumors, but less so in normal tissues. They are both involved in regulating tumorigenesis, development, metastasis processes, correlating with inferior prognosis.Dual targeting of CD73 and AXL can effectively address antigen escape and tumor heterogeneity, representing a promising novel immunotherapy strategy. In this study, combining hypoxia-activated precision with dual-targeting synergy,Investigators have developed a novel CD73/AXL.HypoSti.CAR-T that could effectively expand and survive in hypoxic TME ,offering enhanced efficacy and safety for solid tumors in animal models. Further clinical development is warranted to validate these promising preclinical results. So we conduct this clinical trial in order to test the the safety profiles and anti-tumor activities of CD73/AXL.HypoSti.CAR-T cell in vivo. In dose escalation period, at least 12 eligible patients will be enrolled and receive 3 doses of CD73/AXL.HypoSti.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 CD73/AXL.HypoSti.CAR-T cell infusion at 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 CD73/AXL.HypoSti.CAR-T cell therapy.

Conditions

• Solid Tumor

Interventions

Type	Name	Description
BIOLOGICAL	CD73/AXL.HypoSti.CAR-T cells	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 a total dose of 15-30mg/kg on day -3 and day -2 .
DRUG	Fludarabine	Administered intravenously at dose of 30mg/m2/d on day -3 and day -2.

Timeline

• Start date: 2025-05-01
• Primary completion: 2027-05-01
• Completion: 2028-05-01
• First posted: 2025-04-22
• Last updated: 2025-04-22

Locations

1 site across 1 country: China