Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas

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Trial Details

Sponsor: St. Jude Children's Research Hospital (other)

Phase: 1

Start date: Oct. 30, 2025

Planned enrollment: 42

Trial ID: NCT07222735
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: B7-H3 CAR-T (B7-H3CART, B7-H3-CAR T Cells, TX103, 4SCAR-276, anti-B7-H3 CAR T cells)

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Goal: To establish the safety and tolerability of autologous B7-H3 (CD276) CAR T-cell therapy administered after hypofractionated radiation priming and fludarabine/cyclophosphamide lymphodepletion in children, adolescents, and young adults with relapsed/refractory B7-H3–positive sarcomas, and to generate preliminary signals of antitumor activity and tumor trafficking.

Patients: Patients 21 years or younger with relapsed or refractory B7-H3–positive sarcomas (osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and non-rhabdomyosarcoma soft tissue sarcomas) with evaluable disease including at least one lesion amenable to hypofractionated radiation. B7-H3 positivity is defined by IHC with an H-score of at least 100. Treatment eligibility requires adequate organ function (including LVEF at least 50%, oxygen saturation at least 92% on room air, and prespecified hematologic/renal/hepatic parameters) and performance status at least 60. Key exclusions include intracranial/spinal cord disease, uncontrolled infection, HIV, primary immunodeficiency, rapidly progressive disease, recent radiation (within 4 weeks), and recent therapies that could interfere with CAR activity; systemic steroids above 0.5 mg/kg/day methylprednisolone equivalent are not allowed within 7 days of infusion.

Design: Single-arm, open-label phase I study with a two-step process: eligibility for leukapheresis/manufacturing (or use of a previously collected autologous leukapheresis product) followed by separate eligibility confirmation to proceed to protocol therapy. Participants receive radiation to at least one tumor site with concurrent lymphodepleting chemotherapy, then CAR T-cell infusion, with early safety follow-up focused on the first 4 weeks. Tumor biopsies are incorporated for correlative assessment of trafficking (post-treatment required/expected per protocol language; pre-treatment biopsy optional), and participants meeting criteria may receive optional additional treatment courses.

Treatments: Participants undergo autologous PBMC collection by leukapheresis for manufacturing of B7-H3–directed CAR T cells (or use of banked product). Protocol therapy consists of hypofractionated radiation therapy delivered to at least one disease site, administered in parallel with a single course of lymphodepleting chemotherapy using fludarabine and cyclophosphamide, followed by infusion of autologous B7-H3-CAR T cells. B7-H3-CAR T cells are genetically engineered autologous T cells that recognize the tumor-associated antigen B7-H3 (CD276), which is broadly expressed across many pediatric solid tumors with limited normal-tissue expression; the intent is antigen-specific cytotoxicity and immune activation within tumor sites. Early clinical experience with B7-H3 CAR T-cell platforms in other pediatric/young adult tumors (notably CNS settings using locoregional delivery) has shown feasibility with manageable cytokine-related and neurologic toxicities and occasional objective responses, supporting ongoing evaluation; this trial tests an intravenous strategy in sarcomas combined with radiation priming and lymphodepletion to potentially enhance trafficking and activity.

Outcomes: Primary endpoints are dose-limiting toxicity rate and overall incidence of adverse events through 4 weeks after CAR T-cell infusion, with AEs graded by CTCAE v5.0 and CRS/ICANS graded by ASTCT criteria. Secondary endpoints include best overall response by RECIST v1.1 (and bone marrow evaluation if applicable) assessed approximately 4–12 weeks post-infusion, and evidence of CAR T-cell trafficking to tumor sites assessed by detection of CAR T cells in a post-treatment tumor biopsy around 2 weeks post-infusion.

Burden on patient: High. The trial requires leukapheresis (or provision of a prior product), coordination of hypofractionated radiation and inpatient-typical lymphodepleting chemotherapy, followed by CAR T-cell infusion with intensive early monitoring for CRS/ICANS and other toxicities during the first month. Imaging-based response assessments occur within the first 4–12 weeks, and the protocol includes a post-treatment tumor biopsy with an optional pre-treatment biopsy, adding procedural burden and potential anesthesia needs in younger patients. The need for specialized cellular therapy manufacturing and delivery at a tertiary center, plus close post-infusion safety surveillance, is likely to increase travel and time away from home compared with standard sarcoma care in the relapsed/refractory setting.

Last updated: Jan 2026

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St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

[email protected] / 866-278-5833

Status: Recruiting