Zanidatamab Plus Chemo Shows Response in HER2+ and HER2-Low mBC

By Brandon Twyford - Last Updated: May 16, 2025

Final results from a phase I trial presented at the ESMO Breast Cancer 2025 Annual Meeting support the potential of zanidatamab (Zani), a bispecific HER2-targeted antibody, in combination with chemotherapy for patients with HER2-expressing metastatic breast cancer (mBC), including both HER2-positive and HER2-low subtypes.

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The study, led by Erika P. Hamilton, MD, of Sarah Cannon Research Institute, evaluated the safety and efficacy of zanidatamab plus paclitaxel, capecitabine, or vinorelbine, with some patients also receiving tucatinib. Patients enrolled had previously received multiple lines of systemic therapy, including standard anti-HER2 agents such as trastuzumab (93%), T-DM1 (91%), and pertuzumab (80%).

In total, 46 patients were treated (31 HER2-positive, 15 HER2-low), with a median of three prior lines of systemic therapy. Brain metastases were present in 26% of the cohort, and patients were heavily pretreated, with a subset having received novel HER2-directed agents such as trastuzumab deruxtecan (9%) and tucatinib (9%).

The combination of zanidatamab and chemotherapy was generally well tolerated. Grade 3 or 4 adverse events were reported in 61% of patients, most commonly decreased neutrophil count (24%), neutropenia (9%), and diarrhea (7%). No grade 5 events occurred, and only 4% of patients discontinued treatment due to zanidatamab-related adverse events.

Clinical activity was seen in both HER2-positive and HER2-low populations. Among HER2-positive patients (n=28), the confirmed objective response rate (cORR) was 43%, with a median duration of response (DoR) of 14.8 months and median progression-free survival (PFS) of 10.4 months. In the HER2-low cohort (n=15), the cORR was 20%, with a median DoR of 10.4 months and median PFS of 3.7 months.

“Zani + chemo had a manageable safety profile and good tolerability with promising antitumor activity and durable responses in heavily pretreated pts with HER2-expressing mBC,” the authors wrote.

Reference:

Hamilton EP, et al. Zanidatamab (Zani) + chemotherapy (Chemo) for patients (Pts) with HER2-expressing metastatic breast cancer (mBC): Final results of a phase I trial. Abstract 303MO. Presented at the 2025 ESMO Breast Cancer Annual Congress, May 14-17, 2025; Munich, Germany.

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