SHR-A1811 Plus Pertuzumab Improves Survival in HER2-Positive Metastatic Breast Cancer

SHR-A1811 (Jiangsu Hengrui Pharmaceuticals Co, Ltd) in combination with pertuzumab (Perjeta; Genentech) showed favorable efficacy and safety in patients with HER2-positive (HER2+) unresectable metastatic breast cancer (mBC) in a phase 1b/2 trial (NCT05353361). The data were presented at the European Society For Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.¹

HER2 is the most common BC subtype, accounting for nearly 70% of all diagnoses. Antibody drug conjugates (ADCs) are a crucial cornerstone for the treatment of patients with BC with HER2 alterations. Due to the aggressive, challenging nature of this HER2+ mBC, continued research, development, and improvement of agents is necessary.²

SHR-A1811 is a novel HER2-targeting ADC comprised of trastuzumab linked to a topoisomerase I inhibitor payload via a cleavable linker. As a monotherapy, SHR-A1811 demonstrated promising antitumor activity (NCT04446260). In this phase 1b/2 open-label, multicenter trial presented at ESMO, SHR-A1811 led to favorable patient outcomes in combination with various agents. The efficacy and safety data presented involve the SHR-A1811 plus pertuzumab cohort.^3,4

A study evaluated the safety and efficacy of SHR-A1811 plus pertuzumab in patients with HER2+ unresectable or mBC. In the dose-escalation phase (1b), eligible patients (n = 10) previously received trastuzumab with chemotherapy and at least 1 prior metastatic-setting therapy. Participants received intravenous SHR-A1811 at doses of 3.2 mg/kg, 4.8 mg/kg, or 6.4 mg/kg every 3 weeks alongside standard-dose pertuzumab.³

In the phase 2 expansion (n = 65), the regimen was assessed in patients who either presented with de novo metastatic disease or experienced relapse more than 12 months after completing (neo)adjuvant therapy. The primary end points included safety and overall response rate (ORR).³

As of March 31, 2025 with a median follow-up of 22.2 months (range, 3.1–31.8 months), no dose-limiting toxicities were observed in the dose-escalation cohorts, supporting further evaluation of all 3 dose levels.³

In phase 2, ORR was 63.6% in the 3.2 mg/kg group, 86.4% in the 4.8 mg/kg group, and 84.4% in the 6.4 mg/kg group. Twelve-month progression-free survival rates were similarly strong at 100%, 90.5%, and 96.4%, respectively.³

The combination demonstrated manageable toxicity. Decreased neutrophil count was the most common treatment-related adverse event, occurring in 86.7% of patients, with over half experiencing grade 3 or higher neutropenia. Importantly, no treatment-related deaths or cases of interstitial lung disease were reported.³

Findings from this phase 1b/2 study suggest that SHR-A1811 combined with pertuzumab produces high response rates and durable disease control, with a safety profile consistent with known ADC-based regimens. The strong efficacy signals across dose levels support continued investigation of this combination as a potential new therapeutic option for patients with advanced HER2+ disease.

REFERENCES

1. A phase Ib/​II study of SHR-A1811 injection in breast cancer. Clinicaltrials.gov. Updated September 15, 2023. Accessed November 13, 2025. https://clinicaltrials.gov/study/NCT05353361

2. HER2-negative breast cancer. Cleveland Clinic. Updated February 26, 2025. Accessed November 14, 2025. https://my.clevelandclinic.org/health/diseases/her2-negative-breast-cancer 

3. Huang X, Zhang Q, Liao L, et al. 536MO - SHR-A1811 plus pertuzumab in human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic breast cancer: Results from a phase Ib/II study. Presented at: European Society For Medical Oncology 2025 Congress. October 17-21, 2025. Berlin, Germany. Abstract 536MO

4. A study of SHR-A1811 in subjects with advanced malignant solid tumors. Clinicaltrials.gov. Updated September 15, 2025. Accessed November 14, 2025. https://clinicaltrials.gov/study/NCT04446260