Multicenter phase 3 trial of neoadjuvant anbenitamab and HB1801 in HER2-positive breast cancer

Anbenitamab is a HER2-biparatopic antibody that induces profound receptor clustering, and HB1801 is a solvent-free albumin-bound docetaxel. A phase 3 trial at 61 hospitals in China evaluated neoadjuvant anbenitamab plus HB1801 in patients with stage II or III HER2-positive breast cancer. Patients were randomized 1:1 to receive 6 cycles of neoadjuvant anbenitamab plus HB1801 with or without carboplatin (investigational group; n=263) or trastuzumab, pertuzumab, and docetaxel, with or without carboplatin (control group; n=258). The primary endpoint was total pathological complete response (tpCR) assessed by a blinded independent review committee. The tpCR rate was significantly higher in the investigational group than in the control group (62.4% versus 51.2%; p=0.004). Benefit was consistent across subgroups, including patients with HR-positive disease (51.7% versus 44.4%), HR-negative disease (76.3% versus 59.5%), early-stage disease (63.8% versus 51.9%), locally advanced disease (59.6% versus 50.0%), with carboplatin treatment (66.7% versus 54.5%), and without carboplatin treatment (59.2% versus 48.6%). Grade 3 or 4 treatment-related adverse events occurred in 29.3% of patients in the investigational group and 28.3% of patients in the control group. No treatment-related deaths occurred. The authors conclude that the investigational treatment significantly improved the tpCR rate compared with standard therapy for HER2-positive breast cancer, with a highly manageable safety profile. Long-term survival analyses are warranted (visual abstract).