SHR-A1811 Demonstrates Promising Efficacy and Safety in Neoadjuvant HER2+ Breast Cancer

SHR-A1811 (Jiangsu Hengrui Pharmaceuticals Co, Ltd) for early-stage HER2-positive (HER2+) breast cancer (BC) in the neoadjuvant setting demonstrated promising antitumor activity and favorable safety, according to data from the MUKDEN 07 trial (NCT05635487).¹ The data were presented at the European Society For Medical Oncology 2025 Congress in Berlin, Germany.

HER2+ BC is one of the most common BC subtypes, marked by poorer prognoses and increased risk of recurrence. Antibody drug conjugates (ADCs) are a crucial component of therapy for patients with HER2+ BC, demonstrating capabilities in improved survival and therapeutic response. Despite their success, there is always a need for agents with higher curative potential.²

SHR-A1811 is a novel third-generation HER2-targeting ADC with promising antitumor activity. In the multi-cohort, multicenter, phase II MUKDEN 01 trial, researchers assessed the safety and efficacy of SHR-A1811 as a monotherapy and in combination with pyrotinib (Irene; Jiangsu Hengrui Medicine), a Tyrosine kinase inhibitor that is approved in China for treatment of patients with HER2+ metastatic BC.²

The trial included 64 female patients ages 18 to 75 years with newly diagnosed, untreated stage 2–3 HER2+ BC who were eligible for 6 cycles of neoadjuvant SHR-A1811. Most patients presented with T2 tumors (81.3%), lymph node involvement (65.6%), and were classified as having stage 2 (78.1%) or stage 3 (21.9%) disease.²

Of the population, 29 patients received SHR-A1811 monotherapy and 35 received SHR-A1811 plus pyrotinib. SHR-A1811 was administered as a monotherapy at 4.8 mg/kg every 3 weeks, or in combination with pyrotinib, with varying doses of both agents.²

The trial’s primary end point was total pathologic complete response (tpCR; ypT0-is/ypN0). Secondary end points included breast pathologic complete response (bpCR; ypT0-is), residual cancer burden (RCB), objective response rate (ORR), and safety.²

The tpCR rate was 72.4% (21/29; 95% CI, 52.8–87.3) in the SHR-A1811 monotherapy group and 77.1% (27/35; 95% CI, 59.9–89.6) in the combination therapy group. Among patients receiving monotherapy, the bpCR, RCB 0/I, and BORR rates were 75.9%, 86.2%, and 93.1%, respectively, compared with 77.1%, 85.7%, and 91.4%, respectively, for those receiving combination therapy.²

No new safety signals were identified. The most common grade 3 or higher treatment-related adverse events were decreased neutrophil count (34.5%) in the monotherapy group and decreased neutrophil count (62.9%), diarrhea (42.9%), and decreased white blood cell count (37.1%) in the combination therapy group. No treatment-related deaths were reported.²

Findings from the MUKDEN 07 trial suggest that SHR-A1811, both as a single agent and in combination with pyrotinib, offers substantial antitumor activity and manageable toxicity. The high rates of tpCR and bpCR observed indicate that SHR-A1811 may represent a promising next-generation ADC option in the neoadjuvant setting. Continued follow-up and larger confirmatory trials will be essential to determine its potential to further improve cure rates and redefine treatment standards in HER2-targeted therapy.

REFERENCES

1. A study of SHR-A1811 monotherapy or combined with pyrotinib maleate as neoadjuvant treatment in HER2-positive breast cancer patients. Updated July 5, 2024. Accessed November 7, 2025. https://clinicaltrials.gov/study/NCT05635487

2. Liu C, Gu X, Qiu F, et al. 306P - Neoadjuvant SHR-A1811 with or without pyrotinib in HER2-positive breast cancer (MUKDEN 07): A multi-cohort, multicenter, phase II clinical trial. Presented at: European Society For Medical Oncology 2025 Congress. October 17-21, 2025. Berlin, Germany. Abstract 306P