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

DESTINY-Lung03 is an open-label, multi-arm, phase 1b study. Part 1 evaluated trastuzumab deruxtecan (T-DXd, 4.4 or 5.4 mg/kg) plus durvalumab (1120 mg) and cisplatin (60 or 75 mg/m2; 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

At data cutoff (April 1, 2024), 11, 24, and 36 patients received treatment in Arms 1A, 1B, and 1D, respectively. DLTs reported in Arm 1A: febrile neutropenia (n = 1; grade [G] 5; 4.4 mg/kg/1120 mg/60 mg/m2 doses); decreased platelet count (n = 2; G4 and G5; 5.4 mg/kg/1120 mg/75 mg/m2 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.