Izalontamab brengitecan (Iza-bren; BL-B01D1), a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, for patients with EGFR-mutated NSCLC: Pooled analysis of phase 1 and phase 2 trials
Menée à partir de données de deux essais cliniques de phase I et II incluant au total 171 patients atteints d'un cancer du poumon non à petites cellules avec mutation EGFR (durée médiane de suivi : 20,5 mois), cette étude détermine la dose maximale tolérée de l'izalontamab brengitécan (un conjugué anticorps-médicament ciblant EGFR et HER3) puis évalue son efficacité du point de vue du taux de réponse objective
Background: Therapeutic options after progression on EGFR tyrosine kinase inhibitors (TKIs) remain limited for patients with EGFR-mutated non-small cell lung cancer (NSCLC). Izalontamab brengitecan (Iza-bren; BL-B01D1) is a first-in-class bispecific antibody–drug conjugate targeting EGFR and HER3 with preclinical and early clinical activity.
Patients and methods: We pooled individual patient data from a phase 1a/1b dose-escalation/expansion trial (BL-B01D1-101; (NCT05194982) and a phase 2 multicohort trial (BL-B01D1-203; NCT05880706) in patients with advanced EGFR-mutated NSCLC who had disease progression on prior EGFR TKI therapy. Key endpoints were confirmed objective response rate (cORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. The recommended phase 2 dose (RP2D) was 2.5 mg/kg on days 1 and 8 every 3 weeks.
Results: 171 patients were included (data cutoff 30 June 2025; median follow-up 20.5 months). In the pooled population, cORR was 47.4% (95% CI, 39.7–55.1) and DCR was 81.3% (95% CI, 74.6–86.8); median DoR was 8.5 months (95% CI, 6.9–11.2), median PFS was 6.9 months (95% CI, 5.5–9.6), and median OS was 24.8 months (95% CI, 18.5–not reached). Efficacy at the RP2D (n = 121) was consistent (cORR, 48.8%; DCR, 81.0%; median PFS, 6.9 months; median OS, 24.8 months). In chemotherapy-naïve, post-TKI patients treated at the RP2D (n = 50), cORR was 56.0%, DCR was 90.0%, median DoR was 13.7 months, median PFS was 12.5 months, and median OS was not reached. Treatment-related adverse events (TRAEs) occurred in 98.8% (grade ≥3: 70.2%), predominantly hematologic; interstitial lung disease was rare (0.6%, all grade 1). Discontinuation for TRAEs was 1.2%; no treatment-related deaths were reported.
Conclusions: In this exploratory post hoc pooled analysis, Iza-bren demonstrated promising antitumor activity and a manageable safety profile in heavily pretreated EGFR-mutated NSCLC. These findings are hypothesis-generating and are being further evaluated in ongoing randomized trials.
Annals of Oncology , résumé, 2026