EGFR-HER3-bispecific ADC iza-bren toont activiteit en aanvaardbaar veiligheidsprofiel bij gemetastaseerd borstkanker

BACKGROUND: Bispecific antibody-drug conjugates (ADCs) may overcome limitations of monospecific ADCs. We report results from a phase 1b study of iza-bren, a first-in-class EGFR-HER3 bispecific ADC, in patients with heavily pretreated locally advanced or metastatic breast cancer. PATIENTS AND METHODS: This multicenter study enrolled pretreated patients into three groups: HER2-positive (n=41), hormone receptor-positive/HER2-negative (HR+/HER2-; n=75), and triple-negative breast cancer (TNBC; n=46). Patients received iza-bren 2.5 mg/kg intravenously on days 1 and 8 of each 21-day cycle. The primary endpoint was safety. RESULTS: All 162 enrolled patients were heavily pretreated (69.8% had ≥3 prior lines of therapy). Treatment-related adverse events (TRAEs) occurred in 99.4% of patients, with grade ≥3 events observed in 77.8%, primarily hematologic toxicities (neutropenia 55.6%, anemia 42.0%). Two treatment-related deaths occurred (febrile neutropenia and intracranial hemorrhage). No interstitial lung disease was reported. Confirmed objective response rates were 46.3% (95% confidence interval [CI], 30.7-62.6) in HER2-positive, 37.3% (95% CI, 26.4-49.3) in HR+/HER2-, and 34.8% (95% CI, 21.4-50.2) in TNBC groups, with median progression-free survival of 5.8, 7.0, and 5.8 months, respectively. CONCLUSIONS: Iza-bren exhibited a generally tolerable safety profile and demonstrated clinically meaningful antitumor activity across three major subtypes of heavily pretreated metastatic breast cancer.