Abstract CT012: A phase 2 single-arm open-label trial evaluating zanidatamab in patients with early stage HER2 positive breast cancer: The NeoZanHER Study

Abstract Background: Strategies are needed to de-escalate treatment and avoid chemotherapy in early stage HER2+ breast cancer (BC). We hypothesized that zanidatamab, a highly potent dual HER2-directed bispecific antibody, would be a safe and effective regimen in early stage HER2+ BC. Methods: Patients with 1-3 cm, node negative HER2+ BC were eligible. Patients received 6 cycles (n=11) or 10 cycles (n=9) of zanidatamab (20 mg/kg every 2 weeks) before surgery. Patients with ER+ tumors also received endocrine therapy (n=14). Primary objective was pathologic complete response (pCR). Secondary objectives were pathologic residual cancer burden (RCB) and safety profile. Biomarkers of response were assessed with whole exome sequencing (WES) and RNAseq. Results: Twenty patients were enrolled: fifteen with HER2 IHC 3+, and 5 with HER2 IHC 2+/ISH+ BC. At 6 weeks, zanidatamab treatment resulted in a statistically significant decrease in tumor size and volume by ultrasound (p=0.0005 and p<0.0001, respectively) as well as by MRI (p=0.009 and p=0.0001, respectively). Six patients (30%) had pCR and had 4 limited residual cancer burden (RCB-1; 20%). Treatment was well tolerated with no new safety signals . All patients with pCR had HER2 IHC 3+ tumors, ERBB2 amplification on WES, and PAM50 HER2-enriched subtype. Patients who had pCR had tumors with higher HER2 mRNA expression but this difference did not reach statistical significance (p=0.06). Conclusions: Neoadjuvant zanidatamab demonstrated significant efficacy and manageable safety profile in patients with 1-3 cm , node negative HER2+ BC. De-escalation to HER2-targeted therapy alone may be feasible. Further research is needed to refine patient selection strategies. Citation Format: Vicente Valero, Paula R. Pohlmann, Jason Mouabbi, Xuelin Huang, Wei Qiao, Heather R. Alonzo, Rashmi Krishna Murthy, Gaiane M. Rauch, Taiwo Adesoye, Cristina M. Checka, William F. Symmans, Dmitri Grachev, Flora Alajajyan, Adaeze Nwosu-Iheme, Amy Hassan, Miral Mahesh Patel, Sharon H. Giordano, Kelly Hunt, Debasish Tripathy, Funda Meric-Bernstam. A phase 2 single-arm open-label trial evaluating zanidatamab in patients with early stage HER2 positive breast cancer: The NeoZanHER Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT012.