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 Tumors 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 9 (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.