Phase 2 trial of neoadjuvant anti-HER2 antibody-drug conjugate SHR-A1811 for HR-positive, HER2-low breast cancer

SHR-A1811 is an anti-HER2 antibody-drug conjugate with antitumor activity in patients with HER2-low advanced breast cancer. The phase 2 HELEN-015 trial at The Affiliated Cancer Hospital of Zhengzhou University (China) evaluated SHR-A1811 as neoadjuvant therapy for HR-positive, HER2-low breast cancer. The trial enrolled women aged 18 to 70 years with untreated HR+/HER2-low invasive breast cancer (cT2-3, cN0-3), a Ki-67 proliferation index exceeding 14%, and an ECOG performance status 0 or 1. The patients received intravenous SHR-A1811 at a dose of 6.4 mg/kg every three weeks for eight cycles. The primary endpoint was the objective response rate (ORR). A total of 66 patients were enrolled, with 65 included in the efficacy analysis and 66 in the safety analysis. The ORR was 81.5% (95% CI 70.0-90.1), exceeding the protocol-specified threshold of 66.0%. Pathologic complete response was observed in 2 patients (3.1%; 95% CI 0.4-10.), while 6 patients (9.2%; 3.5-19.6) achieved a residual cancer burden class 0-1. Treatment-related grade 3 or 4 adverse events occurred in 37.9% of patients. No treatment-related deaths or interstitial lung disease were observed. The authors conclude that neoadjuvant SHR-1811 monotherapy achieved favorable response rates with manageable toxicity.