Antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) are widely used for HER2-positive metastatic breast cancer, but their efficacy in the neoadjuvant setting remains under investigation. The MUKDEN 06 trial (NCT05426486), a multicentre, randomised, phase 2b study, compared ARX788 (anti-HER2 ADC) plus pyrotinib (TKI) with the standard neoadjuvant regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCbHP) in female patients with early or locally advanced HER2-positive breast cancer. The primary endpoint was the pathological complete response (pCR, ypT0/is, ypN0) rate, analyzed in the intention-to-treat population. pCR was achieved in 70.6% (48/68) of patients receiving ARX788 plus pyrotinib, compared to 51.5% (35/68) in the TCbHP group, with a significant absolute difference of 19.1% (95% CI, 2.7–34.6; p = 0.023). No treatment-related deaths occurred. The most common grade 3–4 adverse events were diarrhea and hepatic dysfunction in the ARX788 plus pyrotinib

Fondazione Gianni Bonadonna

Combining antibody drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) targeting HER2 has been shown to improve efficacy in patients with advanced HER2+ breast cancer. Here, the authors repor...

In a groundbreaking phase 2b clinical trial published in Nature Communications, researchers have explored an innovative therapeutic approach for HER2-positive breast cancer, comparing the efficacy of a novel antibody-drug conjugate, ARX788, combined with the irreversible tyrosine kinase inhibitor pyrotinib, against the current standard neoadjuvant regimen consisting of trastuzumab, pertuzumab, docetaxel, and carboplatin. The trial’s results not only promise a paradigm shift in targeted treatment strategies but also underscore the potential for more effective and less toxic alternatives for patients battling this aggressive subtype of breast cancer.

The next-generation ADC ARX788 is under investigation in the phase 2 ACE-Breast-03 trial of patients with T-DXd–pretreated HER2-positive breast cancer.

ARX788 was safe and effective in HER2+ advanced breast cancer after disease progression on 1 line of a trastuzumab-based regimen.