AstraZeneca and Daiichi Sankyo’s Enhertu has delivered a statistically significant and clinically meaningful improvement in progression-free survival in patients with HER2-mutant advanced non-small cell lung cancer, according to positive Phase III trial results.

 

The DESTINY-Lung04 trial found that Enhertu (trastuzumab deruxtecan) significantly improved progression-free survival compared with the global standard of care — platinum-pemetrexed chemotherapy combined with pembrolizumab — when used as a first-line treatment.

 

The result makes Enhertu the first and only HER2-directed medicine to demonstrate a progression-free survival benefit over the global standard of care in a Phase III trial in this setting, the companies said.

 

The trial will continue to assess secondary endpoints, including overall survival.

 

HER2 mutations occur in an estimated 2% to 4% of patients with non-small cell lung cancer, a disease that accounts for about 85% of all lung cancer cases. Patients with metastatic NSCLC face a particularly poor prognosis, with only around 10% surviving beyond five years after diagnosis.

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Our oncology pipeline continues to advance with DESTINY-Lung04 becoming the first Phase III trial to demonstrate a progression-free survival benefit versus the global standard of care in this first-line setting, supporting the potential for Enhertu to move earlier in the treatment of HER2-mutant non-small cell lung cancer. 

 

"This aggressive lung cancer often affects younger patients and has historically had limited first-line targeted treatment options, making these positive results an important step forward in bringing additional effective therapies to patients at metastatic diagnosis when there is the greatest opportunity to improve outcomes.”

 

John Tsai, Global Head, R&D, Daiichi Sankyo, said: “Enhertu is already established as the first and only antibody drug conjugate for the second-line treatment of HER2-mutant metastatic non-small cell lung cancer. The positive results seen in DESTINY-Lung04 show that treatment with Enhertu in the first-line setting delays disease progression compared to the global standard of care, highlighting its potential to improve outcomes for patients earlier in the treatment of metastatic disease.”

 

The safety profile was generally consistent with what is already known about Enhertu, with no new safety concerns identified, according to the companies.

 

The global, randomised, open-label DESTINY-Lung04 trial enrolled 454 patients across sites in Asia, Europe and North America. Participants had unresectable, locally advanced or metastatic non-squamous NSCLC carrying a HER2 exon 19 or 20 mutation and were randomly assigned to receive either Enhertu or standard treatment.

 

The primary endpoint was progression-free survival assessed by blinded independent central review. Secondary measures include overall survival, response rates, duration of response and safety.