Allogeneic B7-H3-Targeted CAR Vδ1T-cell Therapy in Advanced Solid Tumors: A Phase I Study

Clinical Snapshot

Key Findings

• P Value: Not reported for efficacy endpoints

• Effect Size: 0% objective response rate by RECIST v1.1 criteria

• Primary Outcome: Manageable safety profile with no GVHD, two grade 1 cytokine release syndrome events, one grade 3 pneumonitis DLT

• Nnt Or Sensitivity: Not applicable - no therapeutic benefit demonstrated

• Confidence Interval: Not reported

Clinical Application

Limited to specialised cancer centres with CAR-T cell therapy capabilities and extensive supportive care infrastructure Not applicable for routine practice; would require TGA approval and PBS listing. Currently experimental with no demonstrated efficacy. Australian CAR-T centres could consider for future research protocols. Highly selected patients with advanced B7-H3-positive solid tumors in research settings only

Abstract

PURPOSE: The aim of the study was to evaluate the safety, pharmacokinetics, and preliminary clinical activity of UTAA06, an "off-the-shelf" allogeneic B7-H3-targeted chimeric antigen receptor (CAR) Vδ1T-cell therapy, in patients with pretreated, advanced B7-H3-positive solid tumors. PATIENTS AND METHODS: In this first-in-human, phase I, dose-escalation study (NCT06372236), 10 patients with advanced solid tumors (including gastric, colorectal, hepatocellular, ovarian, and neuroendocrine cancers) were enrolled. Following lymphodepletion chemotherapy (cyclophosphamide and fludarabine), patients received UTAA06 infusion across three dose levels (5 × 108, 8 × 108, or 1 × 109 cells). The primary endpoint was safety. Secondary endpoints included pharmacokinetics and antitumor efficacy. RESULTS: UTAA06 demonstrated a manageable safety profile; no GVHD was observed, and cytokine release syndrome was limited to two transient grade 1 events. A single dose-limiting toxicity (grade 3 pneumonitis) was reported in one patient at the 5 × 108 cell dose level. Although UTAA06 demonstrated signals of biological activity, including transient reductions in serum tumor markers in 50% of patients, no objective response by RECIST v1.1 criteria was observed. Further analysis identified that the limited CAR T-cell persistence was likely driven by subclinical host-versus-graft rejection. CONCLUSIONS: This study provides clinical proof of concept for allogeneic B7-H3-targeted CAR-Vδ1T cells as a safe platform with low risk of GVHD and demonstrable biological activity in solid tumors. However, clinical efficacy was constrained by limited cellular persistence caused by host immune rejection. Future strategies are required to enhance the durability and therapeutic potential of this allogeneic approach.

References

1. 1.Liu, C., Li, J., Liu, D., Zhang, P., Zhang, M., Xue, R., Gong, J., Liu, L., Tao, M., Cheng, S., Xu, T., Yuan, J., Cao, Y., Wang, Z., Wang, Y., Zhou, J., Lu, M., Peng, Z., Lu, Z., Li, J., Zhang, X., Wang, T., Wang, M., Jiang, L., Meng, H., Yang, L., Qi, C., & Shen, L. (2026). Allogeneic B7-H3-targeted CAR Vδ1T-cell therapy in advanced solid tumors: A phase I study. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-4600