NCT05681650

HER2 Targeted HypoSti.CAR-T Cells in HER2 Positive Advanced Solid Tumors

Phase I/II Clinical Trial of HER2 Targeted HypoSti.CAR-T Cells in Treating Patients With HER2 Positive Local Advanced or Metastatic Solid Tumors

• Status: 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

Chimeric antigen receptor modified T (CAR-T) cell therapy still has multiple difficulties in solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity. In this study, investigators developed a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) that could enable CAR-T cell effectively expand and survive in hypoxic tumor microenvironment. After accomplishment of animal model verification, investigators conduct this clinical trial in order to assess the in vivo safety, feasibility and efficacy of HypoSti.CAR-HER2 T cells in HER2 antigen positive advanced solid tumors.

Detailed description

Currently, chimeric antigen receptor modified T (CAR-T) cell therapy has achieved a series of achievements in hematological malignancies, however, it still has to face plenty of obstacles in more bulky solid tumors, such as absence of tumor specific antigens, complex immunosuppressive tumor microenvironment, and tumor heterogeneity, which may taken together to restrict the efficacy of CAR-T cells in eliminating solid tumors. Previous studies found that intratumoral hypoxic microenvironment facilitated the development and metastasis of tumor cells. Meanwhile, it was difficult for cytotoxic T cells including CAR-T cells to survive and expand in such a hypoxic microenvironment. In this study, investigators developed a novel hypoxia-stimulated CAR expression system (HypoSti.CAR) that could enable CAR-T cell effectively expand and survive in hypoxic tumor microenvironment,which has been demonstrated in animal models. Based on the preclinical data, investigators will further conduct this clinical trial in order to test the potential of this novel system targeting HER2 antigen in vivo. In dose escalation period, at least 9 eligible patients will be enrolled and receive 5 doses of HypoSti.CAR-HER2 T cell therapy (1 × 10\^6 cells/kg, 3 × 10\^6 cells/kg, 6 × 10\^6 cells/kg,1 × 10\^7 cells/kg, 1.5 × 10\^7 cells/kg) according to the "3+3" principle. In dose expansion period, additional 10 to 21 patients will be enrolled to receive HypoSti.CAR-HER2 T cell therapy at dose of recommended phase 2 dose (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 HypoSti.CAR-HER2 T cell therapy.

Conditions

• HER2 Positive Advanced Solid Tumors

Interventions

Type	Name	Description
BIOLOGICAL	HypoSti.CAR-HER2 T cells	Dose escalation: dose -1 (1×10\^6 cells/kg) ,dose 1 (3×10\^6 cells/kg) , dose 2 (6×10\^6 cells/kg), dose 3 (1×10\^7 cells/kg), dose 4 (1.5×10\^7 cells/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 only in the first infusion of HypoSti.CAR-HER2 T cells

Timeline

• Start date: 2023-10-11
• Primary completion: 2025-12-31
• Completion: 2026-12-31
• First posted: 2023-01-12
• Last updated: 2023-12-12

Locations

1 site across 1 country: China