Final analysis of the DESTINY-Lung02 trial

The final analysis of the DESTINY-Lung02 trial, a dose-blinded phase 2 randomised controlled trial, compared two dosages of the antibody-drug conjugate trastuzumab deruxtecan in heavily pretreated, biomarker-selected, HER2 mutation-positive, non-small cell lung cancer. The main findings highlight an impressive objective response rate of 50% in these heavily pretreated patients, with responses being both deep and durable. The median duration of response was 12 months in both dosage arms, which is particularly noteworthy. The study also showed a significant overall survival benefit, with a median OS of 19 months, which is substantial for this heavily pretreated population.

The adverse events were also a significant part of this analysis, with interstitial lung disease (ILD) being of particular interest. The incidence of ILD was 15% in this patient group, predominantly grades 1 or 2, indicating that this side effect is manageable with timely recognition of symptoms or abnormalities on CT scans. This manageability is reassuring for the continued use of trastuzumab deruxtecan.

These results have paved the way for further evaluation of trastuzumab deruxtecan at a dosage of 5.4 mg per kilogram in a phase 3 randomised controlled trial in the first-line setting. This trial will compare trastuzumab deruxtecan against the current standard of care, chemo-immunotherapy, with results anticipated to be available in 2025.