Pooled analysis of phase 1 and phase 2 trials of izalontamab brengitecan for advanced EGFR-mutated non-small cell lung cancer

Therapeutic options for patients with EGFR-mutated non-small cell lung cancer after progression on EGFR TKIs remain limited. Izalontamab brengitecan (Iza-bren; BL-B01D1) is a first-in-class EGFR-HER3 bispecific antibody-drug conjugate with a cleavable linker and an Ed-04 payload. Pooled individual patient data from a phase 1a/1b dose-escalation and expansion trial and a phase 2 multicohort trial evaluated Iza-bren in 171 patients with advanced EGFR-mutated NSCLC who had disease progression on EGFR TKI therapy. The median follow-up was 20.5 months. In the pooled population, the confirmed objective response rate was 47.4% (95% CI 39.7-55.1) and the disease control rate was 81.3% (74.6-86.8); the median duration of response was 8.5 months (6.9-11.2), the median progression-free survival was 6.9 months (5.5-9.6), and the median overall survival was 24.8 months (18.5-NR). Efficacy at the recommended phase 2 dose was consistent. Treat-related adverse events occurred in 98.8% (grade ≥ 3: 70.2%), predominantly hematologic; interstitial lung disease was rare (0.6%; all grade 1). Discontinuation due to treatment-related adverse events occurred in 1.2% of patients; no treatment-related deaths were reported. The authors conclude that Iza-bren demonstrated promising antitumor activity and a manageable safety profile in heavily pretreated EGFR-mutated NSCLC.