Neoadjuvant treatment with the bispecific antibody zanidatamab eliminated tumors in 30 percent of early-stage HER2-positive breast cancer patients without chemotherapy, according to trial results published in Nature Communications.
The single-arm, open-label Phase 2 NeoZanHER trial enrolled 20 patients with node-negative HER2-positive breast cancer measuring between 1 and 3 centimeters. Fifteen participants had HER2 IHC 3+ tumors, while five presented with HER2 IHC 2+/ISH+ disease. Investigators administered zanidatamab at 20 mg/kg every two weeks across two dosing schedules: 11 patients received six doses and nine received 10 doses. Fourteen patients also received concurrent endocrine therapy.
Ultrasound and magnetic resonance imaging recorded significant decreases in tumor size and volume at six weeks of treatment. At surgery, six patients achieved a pathologic complete response, meeting the trial's prespecified primary efficacy target. Four other patients, representing 20 percent of the cohort, showed limited residual disease classified as residual cancer burden class 1.
Researchers observed consistent genomic and molecular characteristics among all six patients who achieved complete response. Every responder possessed HER2 IHC 3+ tumors, ERBB2 amplification on whole-exome sequencing, and the PAM50 HER2-high molecular subtype, alongside a statistical trend toward higher HER2 mRNA expression with a p-value of 0.06. Investigators noted that the overall treatment regimen was well tolerated.
The University of Texas MD Anderson Cancer Center sponsored the investigator-initiated study, which was registered under identifier NCT05035836. Financial support came in part from Zymeworks and Jazz Pharmaceuticals, alongside Nellie B Connelly Research funds, National Center for Advancing Translational Sciences grants UL1 TR0003167 and UM1 TR0045906, and National Cancer Institute award P30 CA016672.
