BL-B01D1 (EGFR×HER3 ADC) cORR 54–67% in Exon20/HER2-Mutant NSCLC

Iza-bren (BL-B01D1) is an EGFR×HER3 bispecific ADC carrying a topo-I payload (Ed-04) via a tetrapeptide cleavable linker; in a phase Ib expansion (NCT05194982), adults with advanced NSCLC harboring pre-specified drivers—EGFR exon20/non-classical EGFR, HER2, ALK/ROS1/RET fusions, KRAS/BRAF/MET, or SMARCA4—previously treated with available TKIs and ≤1 prior chemotherapy received 2.5 mg/kg on D1/D8 Q3W (n=68/73 evaluable; investigational, not US-approved). Confirmed ORR (cORR) was 66.7% in EGFR exon20/non-classical EGFR (ORR 75%, DCR 100%, mPFS not reached) and 53.8% in HER2-mutant (ORR 61.5%, mPFS 8.4 mo); activity was lower in ALK/ROS1/RET fusions (cORR 15.8%, mPFS 2.8 mo) and mixed KRAS/BRAF/MET (cORR 27.3%, ORR 40.9%, mPFS 6.7 mo), with overall mPFS 6.7 mo and mDOR 7.0 mo (95% CI 5.6–NR). Grade≥3 AEs were mainly hematologic (anemia 88%, leukopenia/thrombocytopenia 74%, neutropenia 73%); discontinuations 2.7%, one grade-2 ILD, no treatment-related deaths—contextually, amivantamab in EGFR exon20 shows ORR ~40% (mDOR ~11 mo), trastuzumab deruxtecan in HER2-mutant NSCLC has ORR ~49% with ILD risk, and 2L sotorasib in KRAS G12C yields ORR 28% and mPFS 5.6 mo (cross-trial differences apply).