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

NCT07227571 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1125765NCI-2025-08064FH20941
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Osteosarcoma; Recurrent Osteosarcoma; Refractory Osteosarcoma

Keywords

Bones and Joints

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-related unexpected grade 3 or higher toxicity

  Up to 28 days post infusion

• Maximum tolerated dose/recommended phase 2 dose

  Will be defined as the highest T cell dose from among those tested for which the dose limiting toxicity (DLT) rate is closest to 28% and that at least 4 participants have been evaluated at that level. All observed DLT outcomes for toxicity-evaluable participants will be tabulated by dose level. Will employ a novel Bayesian optimal interval design.

  Up to 28 days post infusion

Secondary Outcomes (5)

• Progression free survival

  From initiation of protocol treatment to disease progression or death of any cause, assessed up to 1 year post infusion

• Overall survival

  From initiation of protocol treatment to death of any cause, assessed up to 1 year post infusion

• Overall response rate (ORR)

  Up to 1 year post infusion

• Stable disease (SD) rate

  Up to 1 year post infusion

• Clinical benefit rate

  Up to 1 year post infusion

Study Arms (1)

Treatment (FH-FOLR1 ST CAR T cells)

EXPERIMENTAL

Patients undergo leukapheresis for manufacturing of the FH-FOLR1 ST CAR T cell product on study. Patients will receive lymphodepleting therapy with fludarabine 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 echocardiography or multigated acquisition scan (MUGA), blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may have the option of undergoing tumor biopsy on study.

Biological: FH FOLR1 ST CAR T-cells; Procedure: Leukapheresis; Drug: Fludarabine; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Biopsy Procedure

Interventions

FH FOLR1 ST CAR T-cells BIOLOGICAL

Given IV

Also known as: Anti-FOLR1 CAR-T Cells, FH-FOLR1 CAR T Cells

Treatment (FH-FOLR1 ST CAR T cells)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Treatment (FH-FOLR1 ST CAR T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (FH-FOLR1 ST CAR T cells)

Cyclophosphamide DRUG

Given IV

Also known as: Cytoxan, Neosar, Revimmune, Cycloblastin

Treatment (FH-FOLR1 ST CAR T cells)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (FH-FOLR1 ST CAR T cells)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide ventriculography

Treatment (FH-FOLR1 ST CAR T cells)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Treatment (FH-FOLR1 ST CAR T cells)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CT, CT Scan, CAT Scan, Computed Axial Tomography

Treatment (FH-FOLR1 ST CAR T cells)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI

Treatment (FH-FOLR1 ST CAR T cells)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: PET, PET Scan

Treatment (FH-FOLR1 ST CAR T cells)

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Bx

Treatment (FH-FOLR1 ST CAR T cells)

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 1-75 years at the time of enrollment
• Tissue confirmation of osteosarcoma diagnosis
• Must have received an anthracycline-based regimen or been deemed ineligible to receive this therapy
• Must have at least one of the following in the 6 months prior to trial consent:
• New site of measurable disease by radiographic imaging or histologic confirmation
• New site of evaluable disease by radiographic imaging or histologic confirmation
• Greater than 20% increase in at least one tumor dimension documented by CT/MRI, AND a minimum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included)
• Persistent measurable disease or fludeoxyglucose F-18 (FDG)-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy, and/or chemotherapy)
• All anti-cancer therapy must be discontinued at enrollment/time of apheresis, with the following washout periods observed:
• Chemotherapy and biologic agents: ≥ 7 days prior to enrollment
• Steroid use: All corticosteroid therapy (unless physiologic replacement dosing and/or topical administration (e.g., inhaled or dermatologic) ≥ 7 days prior to enrollment
• Tyrosine kinase inhibitor (TKI) use: ≥ 7 days prior to enrollment
• Antitumor antibody therapy (including immune checkpoint inhibitor) must be ≥ 3 half-lives or 30 days, whichever is shorter, from time of enrollment
• FOLR1 targeting therapy must be discontinued at least 30 days prior to enrollment
• Gene modified cellular therapy: At enrollment, must be at least 30 days from most recent gene modified cell therapy infusion and document no evidence of modified cells in the peripheral blood OR must be at least 60 days from most recent gene modified cell therapy

You may not qualify if:

• Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by PI
• Corticosteroid therapy at a dose equivalent of \> 15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable. For participants weighing ≤ 30 kg, systemic steroids ≥ 0.5 mg prednisone equivalent/kg/day
• Concurrent use of other investigational anti-cancer agents
• Active uncontrolled infection: HIV positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication
• Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that would limit compliance with study requirements
• Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of \> 15 mg prednisone (or equivalent) per day, unless otherwise approved by PI
• Significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, unless approved by PI. Peripheral neuropathy related to diabetes or prior chemotherapy is acceptable
• Pregnant, possibly pregnant or those expecting to conceive or father children for the duration of the trial through 4 months after T cell infusion
• Participants unwilling to provide consent/assent for participation in the study and 15-year follow-up period if CAR T cell therapy is administered
• Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
• Known allergic reactions to any of the components of study treatments

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Washington Research Foundation: collaborator

Study Sites (1)

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Osteosarcoma

Interventions

Leukapheresis; fludarabine; Cyclophosphamide; Magnetic Resonance Spectroscopy; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Cytodiagnosis; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Michelle Choe, MD

  Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fred Hutch Immunotherapy Intake

CONTACT

206-606-4668; immunotherapy@fredhutch.org

Seattle Children's Hospital Immunotherapy Intake

CONTACT

immunotherapy@seattlechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 12, 2025
• Study Start: January 16, 2026
• Primary Completion (Estimated): January 31, 2044
• Study Completion (Estimated): January 31, 2044
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)