NCT07227571

Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Refractory or Recurrent/Progressive Osteosarcoma, FIERCe Trial

FIERCe: FOLR1 Immune Effector Cell Therapy Against Advanced Osteosarcoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 1 Year – 75 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of FH-FOLR1 ST chimeric antigen receptor (CAR) T cells and how well they work in treating patients with osteosarcoma that recurred or spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that has not responded to previous treatment (refractory) or has come back after a period of improvement (recurrent)/is growing, spreading, or getting worse (progressive). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they attack tumor cells. T cells are taken from a patient's blood through a process called apheresis. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells, such as FOLR1, is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by an intravenous infusion. Chemotherapy drugs, such as fludarabine and cyclophosphamide, are given to a patient before the manufactured FH-FOLR1 ST CAR T cells to make room for the CAR T cells in the blood and to enhance the CAR T cell activity in the patient. FH-FOLR1 ST CAR T cells may be safe, tolerable, and/or effective in treating patients with advanced refractory or recurrent/progressive osteosarcoma.

Detailed description

OUTLINE: This is a dose-escalation study of FH-FOLR1 ST CAR T cells. Patients undergo leukapheresis for manufacturing of the FH-FOLR1 ST CAR T cell product on study. Patients receive lymphodepleting therapy with fludarabine intravenously (IV) on days -5 to -2 and cyclophosphamide IV on days -3 to -2. Patients receive FH-FOLR1 ST CAR T cells IV on day 0, 1 or 2 in the absence of unacceptable toxicity. Patients also undergo blood sample collection, and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) throughout the study. Additionally, patients have the option to undergo tumor biopsy on study. Patients will be monitored closely for at least 28 days after receiving CAR T cells. After completion of study treatment, patients are followed up at days 1, 7, 14, 21, 28, and 42, months 2, 3, 6, 12, and 24, then every 6 months for 3 years followed by annually for 10 years. Patients with ongoing FH-FOLR1 ST CAR T cell persistence are also followed up in months 4, 5, 7, 8, 9, 10, 11, 15, and 18.

Conditions

• Advanced Osteosarcoma
• Recurrent Osteosarcoma
• Refractory Osteosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	FH FOLR1 ST CAR T-cells	Given IV
PROCEDURE	Leukapheresis	Undergo leukapheresis
DRUG	Fludarabine	Given IV
DRUG	Cyclophosphamide	Given IV
PROCEDURE	Echocardiography Test	Undergo echocardiography
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy

Timeline

• Start date: 2026-01-16
• Primary completion: 2044-01-31
• Completion: 2044-01-31
• First posted: 2025-11-12
• Last updated: 2026-02-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study