Tokyo, Japan — August 17, 2026
Daiichi Sankyo and AstraZeneca announced positive topline results from the DESTINY-Lung04 Phase 3 trial, showing that Enhertu® (trastuzumab deruxtecan) delivered a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with global standard of care when used as a first-line treatment for patients with HER2-mutant unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). The trial compared Enhertu with platinum-pemetrexed doublet chemotherapy plus pembrolizumab, the established first-line treatment approach in this setting. According to the companies, Enhertu is the first and only HER2-directed medicine to demonstrate a PFS benefit over global standard of care in a Phase 3 trial in this setting. The DESTINY-Lung04 trial will continue as planned to assess secondary endpoints, including overall survival, while the topline findings are expected to be presented at an upcoming medical meeting and shared with global regulatory authorities.
DESTINY-Lung04 Demonstrates First-Line PFS Benefit
The positive DESTINY-Lung04 results represent an important development milestone for HER2-mutant NSCLC, a molecularly defined form of lung cancer affecting approximately 2% to 4% of patients with non-squamous NSCLC. The global Phase 3 study evaluated Enhertu at 5.4 mg/kg against platinum-pemetrexed chemotherapy combined with pembrolizumab in previously untreated patients with unresectable, locally advanced or metastatic disease carrying a HER2 exon 19 or exon 20 mutation. The primary endpoint was PFS assessed through blinded independent central review. The study randomized patients 1:1 between the two treatment groups and enrolled 454 patients across Asia, Europe and North America. While detailed efficacy data have not yet been disclosed, the companies reported that the PFS improvement achieved statistical significance and was clinically meaningful. The trial remains ongoing for secondary outcomes including overall survival, overall response rate and duration of response, which could provide additional evidence for Enhertu’s potential role earlier in the treatment sequence.
Enhertu Targets Unmet Need in HER2 Mutant NSCLC
HER2 mutations represent an important molecular target in lung cancer, particularly because patients with HER2-mutant NSCLC can experience aggressive disease and limited targeted treatment options in the first-line setting. NSCLC accounts for approximately 85% of lung cancer cases, while metastatic disease continues to have a poor prognosis. HER2 mutations have been associated with tumor growth and are reported more frequently among younger patients and people with no smoking history. Patients may also have an increased incidence of brain metastases. The current global first-line standard of care combines immunotherapy and platinum-based chemotherapy, but a substantial proportion of patients do not respond adequately and eventually experience disease progression. Enhertu is designed as a HER2-directed antibody-drug conjugate (ADC), combining a HER2 monoclonal antibody with Daiichi Sankyo’s DXd topoisomerase I inhibitor payload technology. The positive PFS finding therefore supports continued investigation of this targeted approach in patients with HER2-mutant disease.
Advertisement
Daiichi Sankyo and AstraZeneca Expand Enhertu Strategy
The DESTINY-Lung04 result strengthens the broader development strategy for Enhertu, which is already approved across multiple HER2-targetable cancers and treatment settings worldwide. Enhertu is currently approved in more than 80 countries or regions for previously treated metastatic NSCLC with activating HER2 (ERBB2) mutations, based on earlier DESTINY-Lung studies. The new Phase 3 result could potentially support moving Enhertu into the first-line treatment setting for this molecularly defined lung cancer population, subject to further data and regulatory review. The companies said the safety profile observed in DESTINY-Lung04 was generally consistent with the known safety profile of Enhertu, with no new safety concerns identified. Daiichi Sankyo and AstraZeneca continue to evaluate Enhertu as monotherapy, in combinations and through sequential treatment strategies across multiple HER2-targetable cancers, making the latest first-line NSCLC finding another important milestone in the companies’ expanding HER2-directed oncology portfolio.
Source: Daiichi Sankyo press relese
