Enhertu significantly improved PFS as 1L treatment in HER2-mutant advanced NSCLC in the phase 3 DESTINY-Lung04 trial

CAR-T Digest - August 2020

17 August 2026: Enhertu significantly improved PFS as 1L treatment in HER2-mutant advanced NSCLC in the phase 3 DESTINY-Lung04 trial

AstraZeneca and Daiichi Sankyo announced that Enhertu demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus global standard of care as first-line treatment for patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous NSCLC in the phase 3 DESTINY-Lung04 trial
The phase 3 trial evaluated Enhertu (5.4 mg/kg) against platinum-pemetrexed chemotherapy plus pembrolizumab in 454 patients with HER2-mutant non-squamous NSCLC, with PFS as the primary endpoint; the trial met this endpoint, while overall survival and other secondary endpoints remain under evaluation
The findings address a major unmet need in first-line HER2-mutant NSCLC, where platinum-based chemotherapy plus immunotherapy remains the global standard of care, yet many patients experience disease progression and require additional treatment options
Enhertu is a HER2-directed ADC comprising a monoclonal antibody linked to multiple topoisomerase I inhibitor DXd payloads through tetrapeptide-based cleavable linkers, enabling targeted delivery of the cytotoxic payload to HER2-expressing tumor cells
Strategically, the positive DESTINY-Lung04 results support the potential expansion of Enhertu into the first-line HER2-mutant NSCLC setting, building on its established role in previously treated HER2-mutant metastatic NSCLC and further strengthening its position across HER2-driven cancers