STRIvE-02: A First-in-Human Phase I Study of Systemically Administered B7-H3 Chimeric Antigen Receptor T Cells for...

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• B7-H3 is an immunoregulatory protein frequently overexpressed in pediatric solid tumors.
• Limited expression on critical organs makes B7-H3 an attractive target for immunotherapy.
• Chimeric antigen receptor (CAR) T-cell therapy offers a promising approach for targeting B7-H3.

Purpose of the Study:

• To evaluate the safety and tolerability of systemically administered B7-H3-specific CAR T cells in a first-in-human Phase I clinical trial.
• To assess the preliminary efficacy and dose-response relationship of B7-H3 CAR T cells in pediatric patients with relapsed or refractory solid tumors.

Main Methods:

• A standard 3+3 dose escalation design was employed to determine the safety of B7-H3 CAR T cells at various dose levels.
• Sixteen pediatric patients (11-24 years) with relapsed/refractory solid tumors were enrolled.
• Nine patients were treated at dose levels 1 or 2, with safety and CAR T-cell expansion monitored.

Main Results:

• No dose-limiting toxicities were observed during the first infusion across dose levels.
• CAR T cells were detected in peripheral blood, with one instance of CAR T cells colocalizing with tumor cells.
• One patient achieved an objective partial response after a second infusion, which was associated with enhanced CAR T-cell expansion and cytokine release syndrome.

Conclusions:

• B7-H3 CAR T cells are generally tolerable in pediatric patients with solid tumors, with no acute on-target, off-tumor toxicities observed.
• Significant CAR T-cell expansion appears necessary for achieving objective responses.
• Host and tumor microenvironment factors likely play a critical role in treatment outcomes.