WILMINGTON, DE — AstraZeneca and Daiichi Sankyo reported positive Phase III results for ENHERTU in first-line treatment of advanced HER2-mutant non-small cell lung cancer, potentially positioning the drug to move earlier in treatment than its current U.S. indication for previously treated patients.
The DESTINY-Lung04 trial met its primary endpoint, with ENHERTU demonstrating a statistically significant and clinically meaningful improvement in progression-free survival compared with platinum-pemetrexed chemotherapy plus pembrolizumab, the companies reported.
The companies did not provide detailed efficacy results, including the magnitude of the progression-free survival benefit, in the high-level disclosure. The data are expected to be presented at a forthcoming medical meeting and submitted to regulatory authorities.
The trial will continue to evaluate secondary endpoints, including overall survival.
ENHERTU, also known as fam-trastuzumab deruxtecan-nxki, is a HER2-directed antibody-drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. The companies described DESTINY-Lung04 as the first Phase III study to show a progression-free survival benefit over the global standard of care in the first-line HER2-mutant NSCLC setting.
About 2% to 4% of patients with non-small cell lung cancer have tumors carrying a HER2 mutation, according to information cited by the companies. First-line treatment in the metastatic setting generally combines immunotherapy with platinum-based chemotherapy.
Susan Galbraith, AstraZeneca’s executive vice president for oncology hematology research and development, stated that the results support the potential for ENHERTU to move earlier in treatment.
“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,” Galbraith stated.
Daiichi Sankyo Global Head of Research and Development John Tsai stated that the findings indicate first-line ENHERTU delayed disease progression compared with the current standard of care.
The companies reported that ENHERTU’s safety profile in DESTINY-Lung04 was generally consistent with its established profile and that investigators identified no new safety concerns.
ENHERTU is already approved in the U.S. as a monotherapy for adults with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have previously received systemic therapy. That indication was granted accelerated approval based on objective response rate and duration of response, with continued approval potentially contingent on confirmation of clinical benefit.
The drug also carries U.S. indications across several HER2-defined cancers, including multiple breast cancer settings, previously treated HER2-positive gastric or gastroesophageal junction cancer and certain previously treated HER2-positive solid tumors.
The DESTINY-Lung04 findings could expand ENHERTU’s role into the first-line metastatic lung cancer setting if the results support regulatory approval, moving the therapy ahead of the chemotherapy-immunotherapy regimen currently used for these patients.
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