Enhertu tops standard care in first-line HER2 lung cancer trial

AstraZeneca ↗ 2.14% and Daiichi Sankyo announced on Monday that their antibody drug conjugate Enhertu demonstrated a statistically significant improvement in progression-free survival over the current global standard of care as a first-line treatment for patients with HER2-mutant advanced lung cancer, marking the first time a HER2-directed therapy has achieved such a result in a Phase III trial in this setting.sec+1

The DESTINY-Lung04 trial enrolled 454 patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer across sites in Asia, Europe, and North America. Patients were randomized equally to receive either Enhertu or a combination of platinum-pemetrexed chemotherapy plus pembrolizumab, the current standard first-line regimen.astrazeneca+1

A Path Toward First-Line Approval

Enhertu is already approved in more than 80 countries for previously treated metastatic NSCLC harboring activating HER2 mutations. The DESTINY-Lung04 results could now support regulatory submissions to expand the drug's label into the first-line setting.oncodaily+1

"The positive results seen in DESTINY-Lung04 show that treatment with Enhertu in the first-line setting delays disease progression compared to the current global standard of care," AstraZeneca stated in its press release. The companies said they plan to present full data at a future medical meeting and share findings with regulatory authorities worldwide.astrazeneca

The safety profile observed in the trial was consistent with Enhertu's known profile, with no new safety concerns identified. The study will continue to assess secondary endpoints including overall survival and response rates.stocktitan+1

Mixed Day for AstraZeneca's Lung Cancer Pipeline

The positive Enhertu data came alongside a setback for AstraZeneca's pipeline. The company simultaneously announced it is discontinuing the Phase III eVOLVE-Lung02 trial of its bispecific antibody volrustomig in metastatic NSCLC after an independent data monitoring committee concluded the drug was unlikely to demonstrate superiority over Merck's ↘ 0.23% Keytruda (pembrolizumab) plus chemotherapy in patients with PD-L1-negative tumors.clinicaltrialsarena+1

Susan Galbraith, AstraZeneca's executive vice president of oncology R&D, said the company was "disappointed" but would "learn from this trial" while continuing to advance other medicines from its pipeline. Other Phase III volrustomig trials in cervical cancer, head and neck cancer, and mesothelioma will continue as planned.astrazeneca+1

Targeting a Molecular Subset

HER2 mutations occur in approximately 2% to 4% of patients with non-squamous NSCLC and are more common among younger patients, women, and never-smokers. With lung cancer accounting for an estimated 2.6 million new cases globally in 2024, even a small molecular subset represents a substantial patient population with limited targeted options.blockonomi+1

AstraZeneca shares rose in early Monday trading following the announcements.wsj