Phase I summary of the C406 (CART) efficacy and safety for an HER-2–positive breast cancer population.

Abstract

1025 Background: C406 is a chimeric antigen receptor (CAR) modified autologous T cell, which is a CART targeting HER-2. Here we present the breast cancer results in Phase 1 study. Methods: This phase 1 trial to evaluate the safety and efficacy of chimeric antigen receptor (CAR) modified autologous T cells (C406) for pts with Her2-positive recurrent or refractory breast cancer. C406 is administered intravenously at a fixed dose. Response was evaluated by RECIST v.1.1 every 4 weeks. Results: As of Jan 18, 2025, 8 (F) breast cancer pts have received C406 at doses of 3*10 7 /kg (n = 6), 1*10 8 /kg (n = 2). Two patients in the 3*10 7 /kg -dose group received the second transfusion. Overall, the median age was 59 years, the median number of priortreatment lines was 3.125 and the median number of anti-HER-2 treatment lines was 2. The histological type was invasive breast cainoma, 7 cases of ductal carcinoma and 1 case of mucous carcinoma. These breast cancer hormone receptor types include ER+/PR+, ER-/PR-, and ER+/PR-. Cyclophosphamide combined with fludarabine was the regimen for lymphocyte clearance in all patients. Among them, 1 patient did not receive bridging therapy. Bridging treatment options for other patients were as follows, attillizumab bridging therapy (n = 1), albumin-bound paclitaxel combined with carboplatin and attillizumab (n = 1), albumin-bound paclitaxel combined with Attillizumab (n = 2), gemcitabine combined with attillizumab (n = 1), Albumin-bound paclitaxel + epirubicin + cyclophosphamide + Attilizumab + local radiotherapy (n = 1), docetaxel + Attilizumab + local radiotherapy (n = 1). Among the 8 pts having imaging tumor assessment, the DCR was 75%, which includes 0 partial responses (PR), 6 stable disease (SD), and 2 progressive disease (PD) according to RECIST v1.1. Among the 6 SD pts, 1 pt’s progression-free survival (PFS) is 8 months. All the 8 pts experienced a treatment related adverse events (TRAEs). The most common TRAEs included white blood cell count decrease (100%, 8/8), neutrophil count decrease (100%, 8/8), lymphocyte count decrease (100%, 8/8) and cytokine release syndrome (25%, 2/8). No TRAE leading to discontinuation and death. Conclusions: C406 therapy showed an acceptable safety profile anti-tumor activity for advanced HER-2 positive breast cancer, but the antitumor activity needs to be further explored. Clinical trial information: ChiCTR2500096093 .