Phase 2 trial of zanidatamab in patients with early stage HER2-positive breast cancer

Strategies are needed to avoid chemotherapy in early stage HER2-positive breast cancer (HER2+ BC). The phase 2 NeoZanHER trial, at MD Anderson Cancer Center (Houston, TX) evaluated neoadjuvant therapy with zanidatamab, a dual HER2-directed bispecific antibody, in patients with 1-3 cm, node-negative HER2+ BC. Primary endpoint was pathologic complete response (pCR). Fifteen patients with HER2 IHC 3+ and 5 with HER2 IHC 2+/ISH+ BC were enrolled. Patients received zanidatamab 20 mg/kg every 2 weeks for 6 (n=11) or 10 (n=9) doses. Fourteen patients also received endocrine therapy. At 6 weeks, there was a significant decrease in tumor size and volume. At surgery, six patients (30%) had pCR, meeting the prespecified target, and four (20%) had limited residual cancer burden (RCB-1). Treatment was well tolerated. All patients with pCR had HER2 IHC 3+ tumors, ERBB2 amplification on whole exome sequencing, PAM50 HER2-high subtype, and a trend towards higher HER2 mRNA expression (p=0.06). The authors conclude that de-escalation to HER2-targeted therapy alone may be feasible.