AstraZeneca is discontinuing its Phase III eVOLVE-Lung02 trial after an independent data monitoring committee determined that volrustomig plus chemotherapy was unlikely to beat pembrolizumab plus chemotherapy on either progression-free survival (PFS) or overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients whose tumors express PD-L1 below 1%, the primary analysis population. The trial had enrolled 895 patients across 25 countries to test volrustomig, a bispecific antibody blocking both PD-1 and CTLA-4, as first-line therapy for patients with lower PD-L1 expression. No new safety signals emerged. Susan Galbraith, AstraZeneca's Executive Vice President of Oncology Haematology R&D, said the company is "disappointed" but will "learn from this trial" while continuing other volrustomig Phase III studies in cervical cancer, head and neck squamous cell carcinoma, and mesothelioma .
The setback came alongside two pieces of positive news elsewhere in AstraZeneca's lung cancer pipeline. The Phase III SAFFRON trial showed that Tagrisso (osimertinib) combined with Orpathys (savolitinib) produced statistically significant, clinically meaningful improvements in both PFS and OS versus platinum-based chemotherapy in EGFR-mutated NSCLC patients who had progressed on Tagrisso and developed MET overexpression or amplification — the first global Phase III trial to show such benefit in this resistance setting. The 338-patient trial's safety profile matched each drug's known profile, and AstraZeneca plans to present the data and submit them to regulators, building on the combination's existing China approval.
Separately, the Phase III DESTINY-Lung04 trial found that Enhertu (trastuzumab deruxtecan), developed with Daiichi Sankyo, significantly improved PFS versus the global standard of care — platinum-pemetrexed chemotherapy plus pembrolizumab — as first-line treatment for HER2-mutant non-squamous NSCLC, marking the first HER2-directed therapy to beat standard of care in this setting. The 454-patient trial will continue to assess OS as a secondary endpoint. Galbraith called it "an important step forward," noting HER2-mutant NSCLC, found in 2-4% of patients, often strikes younger patients with limited first-line options. Enhertu's safety profile was consistent with prior data, and results will be shared with regulators.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox!
Sign up now!