Abstract PS3-07: SHR-A1811 as Neoadjuvant Treatment in Patients with HR-Positive, HER2-low Breast Cancer: The first-stage results from an open-label, single-arm, two-stage, phase II clinical trial

Abstract Background: Patients with Hormone receptor (HR)-positive, human epidermal growth factor receptor 2(HER2)-negative breast cancer exhibit lower rates of achieving pathologic complete response (pCR) to neoadjuvant chemotherapy or endocrine therapy, with pCR rates of 10% and 5% respectively. HER2-low breast cancers are enriched in HR-positive breast cancers, but HER2-low patients had significantly lower pCR than those with HER2-0. The anti-HER2 ADC drug T-Dxd has demonstrated anti-tumor activity in HR+/HER2-low advanced breast cancer, based on the DESTINY-Breast 06 study. SHR-A1811, a novel anti-HER2 ADC, has also shown activity in HER2-low advanced breast cancer. Here we conducted this clinical trial to investigate the efficacy and safety of SHR-A1811 as a neoadjuvant treatment in patients with HR+/HER2-low breast cancer. Methods: This was an open-label, single-arm, phase II clinical trial based on Simon's two-stage design. A total of 66 subjects were required for enrollment, with 35 subjects included in the first stage. If 18 or more patients having response, the trial would proceed to the second stage, enrolling an additional 31 subjects. Main inclusion criteria include: aged 18-70 years, treatment-naïve, histologically confirmed invasive breast cancer, cT2-3/N0-2M0, HR+/HER2-low and Ki67>14%. Eligible patients received SHR-A1811 (6.4 mg/kg IV q21 days) for eight cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, residual cancer burden (RCB) 0-1 and pCR. Results: As of June 17, 2024, 34 out of 35 patients in the first stage successfully received the study regimen and finished the operation on schedule. Of all patients, 74.3% (26/35) had node-positive disease, 85.7% (30/35) with stage IIA/IIB, 14.3% (5/35) with stage IIIA at baseline. 74.3% (26/35) patients had baseline HER2 expression of IHC 2+, 25.7% (9/35) were IHC 1+. Our primary endpoint of the first stage was met, with 74.3% (26/35) of patients achieving an ORR, including 26 partial responses and 9 stable diseases. None of the patients achieved pCR. Treatment-related adverse events (TRAEs) were reported in all 35 patients, and the incidence of grade ≥3 TRAEs was 65.7% (23/35), the most common grade ≥3 TRAEs including neutropenia (48.6%,17/35), leukopenia (28.6%,10/35), anemia (22.9%, 8/35), diarrhea and platelet count decreased (11.4%, 4/35). Primary G-CSF prophylaxis was administered to 13 patients, and no grade 3 or higher neutropenia was reported. No interstitial lung disease (ILD) and treatment-related deaths were reported. Conclusions: SHR-A1811 has demonstrated promising anti-tumor activity and an acceptable safety profile as neoadjuvant treatment for patients with HR+/HER2-low breast cancer. The second stage is ongoing, Clinical trial information: NCT05911958. Citation Format: Zhenzhen Liu, Jianghua Qiao, Chengzheng Wang, Xianfu Sun, Min Yan, Lianfang Li, Xiuchun Chen, Jiujun Zhu, Jianfei Wang. SHR-A1811 as Neoadjuvant Treatment in Patients with HR-Positive, HER2-low Breast Cancer: The first-stage results from an open-label, single-arm, two-stage, phase II clinical trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS3-07.