Neoadjuvant anti-HER2 antibody-drug conjugate SHR-A1811 in Hormone Receptor-positive, HER2-low Breast Cancer: A Phase 2 Clinical Trial (HELEN-015).

As an anti-HER2 antibody-drug conjugate, SHR-A1811 has exhibited significant antitumor activity in patients with HER2-low advanced breast cancer. This trial aims to explore the efficacy and safety profile of SHR-A1811 as a neoadjuvant therapy for hormone receptor-positive, HER2-low (HR + /HER2-low) breast cancer. We conducted a single-arm, phase 2 study enrolling women aged 18 to 70 years with untreated HR + /HER2-low invasive breast cancer (cT2-3, cN0-3) and a Ki-67 proliferation index exceeding 14%. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 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, assessed in all patients who received at least one treatment cycle. Secondary endpoints included pathological complete response (pCR, residual cancer burden (RCB) 0-1 rate, event-free survival (EFS), disease-free survival (DFS), and distant disease-free survival (DDFS). In total, 66 of 101 screened patients (65.3%) were enrolled, with 65 included in the efficacy analysis and 66 in safety analysis. The objective response rate was 81·5% (95% confidence interval (CI), 70·0-90·1), exceeding the protocol-specified threshold of 66·0%. Pathological complete response (ypT0/Tis ypN0) was observed in 2 patients (3.1%; 95% CI, 0.4-10.8), while 6 patients (9.2%; 95% CI, 3.5-19.6) achieved a residual cancer burden class 0-1. Treatment-related grade ≥3 adverse events occurred in 37.9% of patients. The most common grade ≥3 adverse events were neutropenia (27.3%), leukopenia (16.7%), and anemia (13.6%). No treatment-related deaths or interstitial lung disease were reported. In summary, SHR-A1811 monotherapy achieved favorable response rates with manageable toxicity, suggesting a potential alternative neoadjuvant option for HR + /HER2-low breast cancer. Further randomized trials may be necessary to assess its clinical value more comprehensively. Follow-up continues for survival. ClinicalTrials.gov identifier: NCT05911958.