A phase 1b/2 trial showed promising results for a new combination therapy in patients with HER2-positive metastatic breast cancer who had already failed treatment with Enhertu.
The study evaluated zanidatamab-hrii, a HER2-targeted bispecific antibody, together with evorpacept, a CD47 blocker, in 24 heavily pretreated patients. Overall, the response rate was 33.3%, but patients with centrally confirmed HER2-positive disease responded much better, achieving a 60% response rate and a median progression-free survival of 8.3 months.
High CD47 expression emerged as a key biomarker. All patients with CD47 levels of at least 20% responded to treatment, with progression-free survival reaching 22.1 months. Researchers also found that responders showed sharp drops in circulating tumor DNA, while resistant tumors carried mutations such as PIK3CA, EGFR, MET, and KRAS.
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