Trastuzumab Deruxtecan in Patients With HER2-Overexpressing NSCLC: Results From Part 1 of the Open-Label, Multicenter, Phase 1b DESTINY-Lung03 Trial

INTRODUCTION: HER2-directed treatments for HER2-overexpressing (HER2-OE; immunohistochemistry [IHC] 3+/2+) NSCLC are needed. METHODS: ; Arm 1A)/carboplatin (area under the plasma concentration-time curve [AUC] 4 or 5; Arm 1B) or T-DXd 5.4 mg/kg monotherapy (Arm 1D) in pretreated metastatic HER2-OE NSCLC. Primary end points: dose-limiting toxicities (DLTs) and adverse events (AEs: Arms 1A and 1B). Secondary end points: safety (Arm 1D) and efficacy (all arms). RESULTS: doses). DLTs reported in Arm 1B: febrile neutropenia (n = 1; G3; 4.4 mg/kg/1120 mg/AUC 5 doses; n = 1; G4; 4.4 mg/kg/1120 mg/AUC 4 doses); decreased platelet count (n = 1; G4; 5.4 mg/kg/1120 mg/AUC 5 doses). Drug-related serious AEs occurred in 63.6%, 37.5%, and 16.7% of Arms 1A, 1B, and 1D, respectively. Confirmed objective response rate (95% confidence interval) per investigator: 37.5% (18.8-59.4; Arm 1B) and 44.4% (27.9-61.9; Arm 1D). CONCLUSIONS: Data confirm the activity of T-DXd monotherapy in pretreated HER2-OE NSCLC but do not support T-DXd plus durvalumab and platinum chemotherapy use in this population. GOV IDENTIFIER: NCT04686305.