Wilmington, Del. — AstraZeneca and Daiichi Sankyo said ENHERTU significantly improved progression-free survival in a Phase III trial evaluating the drug as a first-line treatment for patients with HER2-mutant advanced non-small cell lung cancer.
High-level results from the DESTINY-Lung04 Phase III trial showed ENHERTU, or fam-trastuzumab deruxtecan-nxki, achieved a statistically significant and clinically meaningful improvement in progression-free survival compared with the global standard of care of platinum-pemetrexed chemotherapy plus pembrolizumab.
The trial evaluated patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer, or NSCLC. The study will continue as planned to evaluate secondary endpoints, including overall survival.
About 2% to 4% of patients with NSCLC have tumors with a HER2 mutation. The current first-line standard of care generally combines immunotherapy with platinum-based chemotherapy, but many patients do not respond to treatment or experience disease progression.
“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 1st-line setting, supporting the potential for ENHERTU to move earlier in the treatment of HER2-mutant non-small cell lung cancer,” said Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca. “This aggressive lung cancer often affects younger patients and has historically had limited 1st-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 an antibody-drug conjugate for second-line treatment of HER2-mutant metastatic NSCLC.
“The positive results seen in DESTINY-Lung04 show that treatment with ENHERTU in the 1st-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,” Tsai said.
The companies said ENHERTU’s safety profile in DESTINY-Lung04 was generally consistent with its known profile, with no new safety concerns identified.
Detailed results from the trial will be presented at an upcoming medical meeting and shared with regulatory authorities worldwide.
ENHERTU is a HER2-directed antibody-drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. It is currently approved for previously treated HER2-mutant metastatic NSCLC as well as several other HER2-related cancers.
