Phase 2 Study to Improve Pre-Surgery Treatment for HER2-Positive Early Breast Cancer Using HARPS Biomarker and ctDNA Monitoring

What this Trial Is About

Researchers are investigating neoadjuvant therapy optimization for patients with stage II-III HER2-positive early-stage breast cancer. This phase 2 open-label study uses a novel molecular phosphoprotein-based biomarker assay called HER2 Activation Response Predictive Signature HARPS to identify HARPS-positive and HARPS-negative tumors. The study aims to assess the pathologic complete response rate, 3-year invasive disease-free survival, correlation of circulating tumor DNA ctDNA changes with outcomes, and quality of life changes in patients undergoing adaptive treatment based on HARPS status. Participants with HARPS-positive tumors will receive trastuzumab and pertuzumab for three cycles. Treatment response will be monitored by ctDNA and breast MRI. If responsive, they continue dual HER2-targeted therapy for at least eight cycles before surgery. Non-responders receive added chemotherapy docetaxel, paclitaxel, or Abraxane alongside trastuzumab and pertuzumab before surgery. Patients with HARPS-negative tumors and detectable ctDNA start with a combination of taxane, platinum, trastuzumab, and pertuzumab. If ctDNA clears, they continue the same treatment before surgery if not, therapy escalates to anthracycline-based regimens or trastuzumab deruxtecan as per physician choice. Participants undergo tumor testing for HARPS status and ctDNA collection before treatment. They receive breast MRIs and ctDNA monitoring throughout therapy. Researchers will evaluate treatment-emergent adverse events up to 36 months, invasive disease-free survival over three years, and quality of life measures. The total enrollment is 50 patients, with 25 in each HARPS cohort. The study includes regular visits for treatment administration, monitoring, and surgery, with long-term follow-up to assess outcomes and safety.

Optimize Neoadjuvant Therapy in HER2-Positive Early-Stage Breast Cancer