Trastuzumab Deruxtecan (HER2 ADC) posts 50–56% ORR in HER2-mutant mNSCLC

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody–drug conjugate with a topoisomerase-I payload; in the dose-blinded, randomized Phase 2 DESTINY-Lung02 (NCT04644237), previously treated HER2-mutant mNSCLC patients received 5.4 mg/kg (n=102) or 6.4 mg/kg (n=50) every 3 weeks. Confirmed ORR was 50.0% (51/102) and 56.0% (28/50), median treatment duration 7.7 vs 8.3 months, and health-related quality of life was preserved during therapy; grade≥3 TRAEs occurred in 39.6% vs 60.0%, with adjudicated drug-related ILD in 14.9% vs 32.0% (one grade 5 in each arm), supporting the approved 5.4-mg/kg dose’s benefit–risk. Response rates exceed typical second-line chemo benchmarks—docetaxel±ramucirumab ORR ≈23%, mPFS ≈4.5 mo, mOS ≈10.5 mo—and target a biomarker present in ~2–4% of NSCLC.