Safety and antitumor activity of the first-in-class EGFR-HER3 bispecific antibody-drug conjugate iza-bren (BL-B01D1) in patients with pretreated locally advanced or metastatic breast cancer: a phase Ib study.
J Zhang, Y Meng, Y Du et al.
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In 30 seconds
This multicenter phase Ib study evaluated the safety and antitumor activity of iza-bren, an EGFR-HER3 bispecific antibody-drug conjugate, in 162 patients with heavily pretreated locally advanced or metastatic breast cancer across HER2-positive, HR-positive/HER2-negative, and triple-negative subtypes. Treatment-related adverse events occurred in 99.4%, with grade ≥3 events in 77.8%, mainly hematological. Confirmed objective response rates were 46.3%, 37.3%, and 34.8%, respectively; median progression-free survival was 5.8, 7.0, and 5.8 months.
Key findings
- Grade ≥3 treatment-related adverse events occurred in 77.8%; neutropenia occurred in 55.6% and anemia in 42.0%.
- Confirmed objective response rates were 46.3% in HER2-positive, 37.3% in HR-positive/HER2-negative, and 34.8% in triple-negative disease.
- Median progression-free survival was 5.8, 7.0, and 5.8 months across the HER2-positive, HR-positive/HER2-negative, and triple-negative groups, respectively.
- Two treatment-related deaths occurred; no interstitial lung disease was reported.
Why it matters
The study reports antitumor activity across three major breast cancer subtypes in a heavily pretreated population, while also documenting substantial severe toxicity, particularly hematological events. These results provide early clinical evidence for a bispecific ADC approach, but the phase Ib findings should be interpreted alongside the observed risks and the need for further evaluation.
What to keep in mind
This was a phase Ib study without a comparator, so it cannot establish comparative efficacy or whether iza-bren improves outcomes over other treatments.