STRIVE-02: First-in-Human B7H3 CAR T-Cells for Pediatric Patients With Relapsed/Refractory Solid Tumors

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B7H3-targeting chimeric antigen receptor T (CAR-T) cells elicit anti-tumor activity and are safe for children and young adults (CYA) with relapsed/refractory solid tumors (R/RST), according to results of the phase 1 STRIVE-02 trial (NCT04483778) presented as a poster at the 2022 American Society of Clinical Oncology (ASCO) annual meeting.¹

Investigators sought to evaluate the safety and feasibility of genetically modifying a patient’s own T-cells to express scFV-IgG4hinge-CD28tm-4-1BB-zeta B7H3-specific CAR with the methotrexate resistance/selection cassette DHFRdm and the tracking/suicide construct EGFRt. In order to test out the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T-cells would promote the expansion and persistence of the CAR-T cells, the research team launched 2 study arms: Arm A participants received B7H3-specific CAR T cells only, while Arm B participants received CAR T cells directed at B7H3 and CD19, a marker on the surface of B lymphocytes. Arm A data were presented in the ASCO 2022 poster.

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The open-label, non-randomized study enrolled 16 CYA (age 11-24, median 17 years) with relapsed or refractory non-central nervous system solid tumors. Three participants received dose level (DL) 1 comprising 0.5 x 10⁶ CAR-T/kg and 6 received DL 2 comprising 1 x 10⁶ CAR-T cells/kg. All participants underwent lymphodepletion with fludarabine and cyclophosphamide prior to the CAR-T infusion.

In addition to safety, investigators also tracked maximal tolerated dose and biologically effective dose (BED) by observing toxicity through Day 28 and employing a statistical 3+3 design.

After the first infusion, maximum circulating CAR-T expansion was 4.98 cells/uL (range 0.23-4.98 cells/uL) with median persistence of 28 days (range 14-90). Three of the 9 patients who received the infusion demonstrated best overall response of Stable Disease, and investigators determined DL2 to be the BED.

Investigators observed no dose-limiting toxicities after the first infusion, and the most common side effects, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) dictionary, were fatigue and cytokine release syndrome (CRS) (n = 2, maximum CTCAE grade 2).

One subject who received a second DL2 infusion that resulted in boosted CAR-T expansion of 1590 cells/uL (86% of circulating CD3 cells). The subject experienced CTCAE grade 2 CRS and dose-limiting CTCAE grade 4 liver enzyme elevation that was described as “transient.” The research team observed a partial metabolic response on FDG-PET by PERCIST criteria at Day 28.

“B7H3 CAR T cells are safe and demonstrate anti-tumor activity in CYA with R/RST,” investigators concluded. “CAR-T cell expansion and persistence may be necessary to achieve objective responses. STRIvE-02 Arm B will explore dual expression of CD19 CAR with B7H3 CAR, using lymphocytic CD19 expression to drive CAR expansion and persistence.”

Reference:

Pinto N, Albert CM, Taylor M, et al. STRIVE-02: a first-in-human phase 1 trial of systemic b7h3 car t cells for children and young adults with relapsed/refractory solid tumors. Poster presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Accessed June 6, 2022.https://meetings.asco.org/2022-asco-annual-meeting/14400?presentation=206941#206941