Dr Montero on the Rationale for Evaluating Zanidatamab/Evorpacept in HER2+ Metastatic Breast Cancer

“Evorpacept augments the effect [of antibody-dependent phagocytosis] because it's an anti-CD47 small molecule; [therefore], it increases the ability of the antibody-dependent phagocytosis.”

Alberto Montero, MD, MBA, CPHQ, clinical director of the Breast Cancer Program at University Hospitals, medical director of the Clinical Trials Unit at Seidman Cancer Center, and professor of Medicine at Case Western Reserve University, explains the rationale for evaluating zanidatamab-hrii (Ziihera) plus evorpacept in patients with HER2-positive and HER2-low metastatic breast cancer.

Zanidatamab is a bispecific monoclonal antibody that is directed against HER2, similar to trastuzumab (Herceptin) and other HER2-targeted antibodies, Montero begins. He explains that zanidatamab has an essential mechanism of action through an immune-mediated effect via antibody-dependent phagocytosis.

Therefore, combining zanidatamab with evorpacept increases the effect of antibody-dependent phagocytosis, as evorpacept is an anti-CD47 small molecule, he continues. This rationale supported the evaluation of the combination in a phase 1b/2 study (NCT05027139).

The phase 1b/2 study evaluated the agent with evorpacept in patients with HER2-positive and HER2-low metastatic breast cancer. Early data revealed that patients in cohort 1 (n = 21) with HER2-positive metastatic breast cancer experienced a confirmed overall response rate (ORR) of 33.3% (95% CI, 14.6%-57.0%), which were all partial responses. Of note, the disease control rate was 71.4% (95% CI, 47.8%-88.7%), the median progression-free survival (PFS) was 3.6 months (95% CI, 1.8-11.0), and the median duration of response was not evaluable (range, 3.6-25.9). Among patients from cohort 2 (n = 15) with HER2-low metastatic breast cancer, the confirmed ORR was 20.0% (95% CI, 4.3%-48.1%), and the median PFS was 1.9 months (95% CI, 1.6-3.9).

The study included patients with locally advanced inoperable and/or metastatic HER2-expressing breast cancer identified by local or central laboratory test results, disease progression during or following the most recent regimen of systemic therapy for advanced cancer, measurable disease per RECIST 1.1 criteria, adequate organ function, and an ECOG performance status of 0 or 1.