Trastuzumab Deruxtecan in Patients From China With Pretreated HER2-Mutant Non–Small Cell Lung Cancer: Final Analysis of the Phase 2, Single-Arm DESTINY-Lung05 Trial

Introduction Trastuzumab deruxtecan (T-DXd) was approved in China in October 2024 for previously treated human epidermal growth factor receptor 2 ( HER2 )-mutant (HER2m) unresectable/metastatic non-small cell lung cancer (NSCLC), based on DESTINY-Lung02 and DESTINY-Lung05 primary results. Here, we report the DESTINY-Lung05 final analysis. Methods DESTINY-Lung05 (NCT05246514), an open-label, single-arm, multicenter, phase 2 study, investigated T-DXd (5.4 mg/kg once every 3 weeks) in patients from China with HER2m (locally or centrally confirmed activating HER2 exon 19/20 mutation) metastatic NSCLC with disease progression on/after ≥1 prior anticancer therapy. The primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours 1.1 by independent central review (ICR). Secondary endpoints included progression-free survival (PFS) by ICR, overall survival (OS), and safety. Results As of November 4, 2024, 72 patients with HER2m NSCLC had received T-DXd 5.4 mg/kg; the median duration of follow-up was 20.2 months (range 2-27). Confirmed ORR (ICR) was 56.9% (95% confidence interval [CI] 44.7-68.6). Median PFS (ICR) and OS were 9.9 months (95% CI 7.1-16.5) and 21.0 months (95% CI 17.5-not calculable), respectively. Grade ≥3 drug-related adverse events occurred in 40 (55.6%) patients. Adjudicated drug-related interstitial lung disease/pneumonitis events were observed in nine (12.5%) patients (n=8 grade 1/2; n=1 grade 3). Conclusions With extended follow-up, T-DXd continued to demonstrate clinically meaningful and durable antitumor activity in patients from China with pretreated HER2m metastatic NSCLC, with no new safety signals. Results affirm the use of T-DXd as a treatment option in China for this patient population. Microabstract T-DXd was the first HER2-directed therapy conditionally approved in China for patients with previously treated HER2m unresectable/metastatic NSCLC. Final analysis results from DESTINY-Lung05, an open-label, single-arm, phase 2 study, affirm that T-DXd (5.4 mg/kg) induces durable responses and clinically meaningful survival benefit in patients from China with pretreated metastatic HER2m NSCLC. No new safety signals were observed. These data further support the use of T-DXd (5.4 mg/kg) as a treatment option in China for this patient population.