Multicenter phase 1b study of iza-bren in patients with pretreated locally advanced or metastatic breast cancer

Bispecific antibody-drug conjugates (ADCs) may overcome limitations of monospecific ADCs. A multicenter phase 1b trial in China evaluated iza-bren, a first-in-class EGFR-HER3 bispecific ADC, in patients with heavily pretreated locally advanced or metastatic breast cancer: HER2-positive (n=41), HR-positive/HER2-negative (n=75), and TNBC (n=46). Patients received iza-bren 2.5 mg/kg intravenously on days 1 and 8 of 21-day cycles. All patients were heavily pretreated; 69.8% had ≥ 3 prior lines of therapy. Treatment-related adverse events occurred in 99.4% of patients, with grade ≥3 events in 77.8%; two treatmnet-related deaths occurred (febrile neutropenia and intracranial hemorrhage). No interstitial lung disease was reported. Confirmed objective response rates were 46.3% (95% CI 30.7-62.6) in HER2-positive, 37.3% (26.4-49.3) in HR+/HER2-, and 34.8% (21.4-50.2) in TNBC groups, with median progression-free survival of 5.8, 7.0, and 5.8 months, respectively. The authors conclude that iza-bren exhibited a generally tolerable safety profile and demonstrated clinically meaningful antitumor activity across three major subtypes of heavily pretreated metastatic breast cancer.