Multinational phase 2 study of trastuzumab deruxtecan for metastatic solid tumors harboring activating HER2 mutations

Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody drug conjugate approved by EMA and FDA for HER2-mutant non-small cell lung cancer. The multinational phase 2 DESTINY-PanTumor01 trial evaluated T-DXd for metastatic solid tumors with activating HER2 mutations in previously treated patients. Confirmed objective response rate by independent central review (primary endpoint) was 29.4% (95% CI 20.8-39.3). The median progression-free and overall survival median progression-free and overall survival were 5.4 and 10.9 months, respectively. Treatment-emergent adverse events of grade 3 or worse were seen in 51% of patients (grade 5 in 2%). The authors conclude that T-DXd showed antitumor activity and durable responses in pretreated patients across multiple tumor types with activating HER2 mutations, with no new safety signals.