Abstract

8543 Background: In the DESTINY-Lung02 primary analysis (data cutoff, Dec 23, 2022), T-DXd 5.4 mg/kg and 6.4 mg/kg demonstrated strong and durable responses and an acceptable and generally manageable safety profile in patients with previously treated HER2 ( ERBB2)-mutant ( HER2m) mNSCLC (Goto et al. 2023). We report updated efficacy and safety results from the final analysis of DESTINY-Lung02. Additional analyses, including data on clinically relevant subgroups and patient-reported outcomes, are planned for presentation. Methods: In this randomized, blinded, multicenter, phase 2 trial, patients with previously treated HER2m mNSCLC were randomly assigned 2:1 to receive T-DXd 5.4 mg/kg or 6.4 mg/kg once every 3 weeks. The primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR), and key secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. The study was not powered to statistically compare the 2 doses. Results: Patients were randomly assigned to T-DXd 5.4 mg/kg (n = 102) or 6.4 mg/kg (n = 50). At the final analysis data cutoff (Aug 25, 2023), the median duration of follow-up (range) was 15.8 months (mo) (1.1-28.6) and 16.5 mo (0.6-28.7) with T-DXd 5.4 and 6.4 mg/kg, respectively (additional 8 mo follow-up since last DCO). Updated efficacy results are presented in the table. After a median treatment duration (range) of 7.7 mo (0.7-27.6) and 8.3 mo (0.7-24.0) with T-DXd 5.4 and 6.4 mg/kg, respectively, drug-related grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 39.6% (40/101) and 60.0% (30/50) of patients in each arm. Lower rates of drug-related TEAEs associated with drug discontinuation (14.9% [15/101]), dose reduction (16.8% [17/101]), and drug interruption (30.7% [31/101]) were observed with T-DXd 5.4 mg/kg than 6.4 mg/kg (26.0% [13/50], 34.0% [17/50], and 54.0% [27/50], respectively). Adjudicated drug-related interstitial lung disease (ILD)/pneumonitis was reported in 14.9% (15/101) and 32.0% (16/50) of patients in the T-DXd 5.4 and 6.4 mg/kg arms, respectively; most events were grade 1 or 2 (1 grade 5 event in each arm). Conclusions: In this final analysis, T-DXd 5.4 and 6.4 mg/kg continued to show strong and durable responses, which was consistent with the primary analysis, and no significant changes in toxicity were observed with longer follow-up. The approved T-DXd 5.4 mg/kg dose was associated with a more favorable benefit-risk profile and a reduced incidence of adjudicated drug-related ILD/pneumonitis. Clinical trial information: NCT04644237 . [Table: see text]