NCT07307287

SHR-A1811 Plus Pertuzumab as Neoadjuvant Therapy for Early or Locally Advanced HR-Positive HER2-Positive Breast Cancer: A Prospective, Open-Label, Phase II Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Tianjin Medical University Cancer Institute and Hospital · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Breast cancer is the most common malignancy in women, with approximately 20% classified as HER2-positive. Anti-HER2 blockade (trastuzumab plus pertuzumab) combined with chemotherapy constitutes the standard neoadjuvant regimen; however, the pathological complete response (pCR) rate in the HR-positive subgroup remains only 35-40%, and platinum-containing schedules are associated with significant hematologic toxicity. Antibody-drug conjugates (ADCs) integrate targeted delivery with potent cytotoxic payloads. SHR-A1811 (ruikang-trastuzumab), a domestically developed ADC by Hengrui Pharmaceutical, is conjugated with a topoisomerase I inhibitor (mean drug-to-antibody ratio \[DAR\] ≈ 6). Preclinical data demonstrate that SHR-A1811 exhibits superior efficacy to trastuzumab emtansine (T-DM1) in both trastuzumab-sensitive and resistant HER2-expressing tumor models, with a manageable safety profile. This prospective, open-label, phase II trial will enroll patients with early-stage/locally advanced HR-positive/HER2-positive breast cancer, who will receive neoadjuvant SHR-A1811 plus pertuzumab. At baseline, BluePrint gene profiling will be performed to stratify participants into luminal and non-luminal subtypes: patients with luminal subtype who achieve stable disease (SD) after 4 cycles will switch to a regimen of trastuzumab, pyrotinib, dalpiciclib, and an aromatase inhibitor for an additional 4 cycles; all other patients will continue ADC-based dual-target therapy for 2-4 further cycles, followed by surgical resection. Circulating tumor DNA (ctDNA) dynamics will be dynamically monitored at baseline, after 4 cycles of treatment, and preoperatively to evaluate early treatment sensitivity. The primary endpoint is the pCR rate. Secondary endpoints include event-free survival (EFS), objective response rate (ORR), and safety profiles. Exploratory analyses will investigate the correlation between molecular subtypes and treatment responses, aiming to establish a chemotherapy-free, precision neoadjuvant strategy for HR-positive/HER2-positive breast cancer.

Conditions

• SHR-A1811
• HER2-Postive Breast Cancer
• HR+ Breast Cancer
• Early Breast Cancer
• Locally Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	SHR- A1811	SHR-A1811 4.8 mg/kg and pertuzumab 420 mg are administered intravenously every 3 weeks for 4 cycles as neoadjuvant therapy. Patients with luminal subtype and stable disease (SD) then switch to trastuzumab 6 mg/kg, pyrotinib 320 mg po daily, dalpiciclib 125 mg po days 1-21 of a 28-day cycle, plus an aromatase inhibitor for 4 additional cycles. All remaining patients (PR/CR luminal or any non-luminal) continue SHR-A1811 + pertuzumab for 2-4 more cycles before surgery. Treatment continues until progression, unacceptable toxicity, or surgical resection.

Timeline

• Start date: 2025-12-20
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2025-12-29
• Last updated: 2025-12-29