On August 17, AstraZeneca PLC and Daiichi Sankyo jointly announced that the Phase III DESTINY-Lung04 trial evaluating Enhertu (trastuzumab deruxtecan) as a monotherapy in the first-line treatment of non-small cell lung cancer (NSCLC) achieved highly positive results.

This global, randomized, multicenter, open-label study (n=454) assessed the efficacy and safety of Enhertu compared with standard care—pembrolizumab combined with platinum-based doublet chemotherapy—in patients with unresectable, locally advanced, or metastatic non-squamous NSCLC harboring HER2 exon 19 or exon 20 mutations. The primary endpoint was progression-free survival (PFS).

Findings showed that patients in the Enhertu arm experienced a statistically significant and clinically meaningful improvement in PFS versus those receiving standard treatment. The trial will proceed as planned to evaluate secondary endpoints, including overall survival (OS).

Notably, Enhertu is the first antibody-drug conjugate (ADC) to demonstrate in a Phase III study that monotherapy, as a first-line regimen, improves PFS in NSCLC patients compared with standard care.