Safety and Efficacy of an autologous HER2-Targeting CAR-T therapy in Patients with HER2-positive recurrent or refractory Breast Cancer: An analysis of a Phase I clinical study

Background Chimeric Antigen Receptor (CAR)-engineered T cells constitute a novel immunotherapeutic approach. CAR-T therapy has achieved remarkable breakthroughs in the treatment of hematological malignancies, yet its application to solid tumors confronts enormous challenges. HER2-CAR-T therapy may serve as a promising treatment option for breast cancer patients who have failed anti-HER2 therapy. Here we reported the Phase I clinical trials results of C406 in HER2-positive recurrent or refractory breast cancer. Methods The Phase I was a dose-escalation study to evaluate the safety, efficacy and pharmacokinetics of C406 in breast cancer patients. Patients received a single dose of 3×107cells/kg (Cohort 1) or 1×108cells/kg (Cohort 2) following bridging and lymphodepleting chemotherapy. The primary endpoint was to evaluate the incidence of treatment emergent adverse events. The secondary endpoint was to evaluate the efficacy and pharmacokinetics of C406. The study also explored diversified bridging therapy and conditioning chemotherapy for lymphodepletion. Results By cut-off date of 2025 July 1st, totally 8 patients were enrolled, 6 patients received C406 at a dose of 3×10⁷ cells/kg, and the remaining 2 patients were administered 1×10⁸ cells/kg. Results showed that C406 was well tolerated and demonstrated a favorable toxicity profile. No case of grade 3 or higher cytokine release syndrome. No case of grade 3 or higher CAR-T related adverse events. Grade 3 or higher adverse events were hematological disorders by lymphodepletion therapy. DCR (disease control rate) was 75% and mPFS (median progression-free survival) was 9 weeks. Conclusion In patients with HER2-positive relapsed or refractory breast cancer, C406 has demonstrated a tolerable safety profile, providing a rationale for subsequent research; however, its efficacy requires further confirmation. Trial registration Trial No.MR-37-23-019847. Registered 17 January 2025, https://www.medicalresearch.org.cn.