Iza-Bren Shows Antitumor Activity in Phase Ib Trial of Relapsed Extensive-Stage SCLC

An open-label, multicenter phase Ib dose-expansion study evaluated izalontamab brengitecan (iza-bren; BL-B01D1), an EGFR-HER3 bispecific antibody-drug conjugate, in patients with extensive-stage small cell lung cancer progressing after prior systemic therapies. Patients received 2.5 mg/kg on days 1 and 8 of each 3-week cycle. Primary endpoints were objective response rate and safety/tolerability.

As of December 5, 2024, 52 patients had enrolled. The objective response rate was 48.1% (95% CI, 34.0–62.4), median progression-free survival was 4.1 months (95% CI, 3.0–5.5), and median overall survival was 12.2 months (95% CI, 9.1–13.2). Among 22 patients receiving second-line treatment, the response rate was 72.7% (95% CI, 49.8–89.3), median progression-free survival was 6.2 months, and median overall survival was 15.0 months.

The most common treatment-related adverse events were neutropenia, thrombocytopenia, anemia, and leukopenia; the abstract did not report their frequencies or severity. Exploratory analysis suggested an association between positive HER3 expression and better treatment response. These findings support further evaluation, but the small sample, uncontrolled design, and exploratory biomarker analysis limit clinical interpretation. A randomized phase III comparison with topotecan (NCT06500026) is ongoing.