In the primary analysis of DESTINY-Lung01 (NCT03505710; data cutoff May 3, 2021), T-DXd (a HER2-targeting antibody–drug conjugate) in pts with previously treated HER2m NSCLC had a confirmed objective response rate (ORR) of 55% (95% CI, 44-65) and a safety profile generally consistent with previous reports (Li N Engl J Med 2021). This update provides additional subgroup analyses and longer follow-up in all pts. Pts with HER2m NSCLC refractory to standard therapy received T-DXd 6.4 mg/kg IV Q3W. Primary endpoint was ORR per RECIST v1.1 by independent central review (ICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. At data cutoff (December 3, 2021), 91 pts with HER2m NSCLC were assessed. At baseline, 36.3% had asymptomatic central nervous system metastasis (CNS met); 33.0% had >2 prior therapies; 94.5% had prior platinum-based chemotherapy (CT). Median follow-up and treatment duration were 16.7 and 6.9 mo, respectively. The table shows primary endpoint for the overall and subgroup populations, including pts with CNS met. In the overall population, median PFS was 8.2 mo (95% CI, 6.0-11.9); median OS was 18.6 mo (95% CI, 13.8-25.8); median DOR was 10.6 mo (5.8-17.7); DCR was 92.3% (95% CI, 84.8-96.9). Drug-related treatment-emergent adverse events (TEAEs) occurred in 88 (96.7%) pts. The most common TEAEs were nausea (76.9%), vomiting (47.3%), and alopecia (46.2%). Adjudicated drug-related interstitial lung disease occurred in 25 (27.5%) pts (3 grade [G] 1, 16 G 2, 4 G 3, 2 G 5).Table: 976PT-DXd efficacy in HER2m NSCLCOverall N = 91Prior therapyCT n = 86CT and anti–PD-(L)1 n = 57CNS metHER2 KD mut n = 85≤2 lines n = 61>2 lines n = 30Yes n = 33No n = 58ORR by ICR, n (%) 95% CI50 (54.9) 44.2-65.434 (55.7) 42.5-68.516 (53.3)34.3-71.746 (53.5) 42.4-64.337 (64.9) 51.1-77.118 (54.5) 36.4-71.932 (55.2) 41.5-68.349 (57.6) 46.5-68.3Complete response1 (1.1)NA1 (1.2)001 (1.7)NAPartial response49 (53.8)45 (52.3)37 (64.9)18 (54.5)31 (53.4)Stable disease34 (37.4)34 (39.5)16 (28.1)14 (42.4)20 (34.5)Progressive disease3 (3.3)2 (2.3)1 (1.8)03 (5.2)Nonevaluable4 (4.4)4 (4.7)3 (5.3)1 (3.0)3 (5.2)DOR, median, mo 95% CI10.6 5.8-17.712.0 5.7-18.310.6 5.6-18.3NANA, not available. Open table in a new tab NA, not available. T-DXd showed durable anticancer activity that was consistent across subgroups including pts with >2 prior therapies and pts with CNS met. The updated results show no new safety signals and provide further evidence supporting T-DXd as a new treatment standard in pts with previously treated HER2m NSCLC.