The eVOLVE-Lung02 trial was testing whether volrustomig plus chemotherapy could improve outcomes over the established combination of pembrolizumab and chemotherapy in previously untreated patients with metastatic NSCLC and low PD-L1 expression.
An Independent Data Monitoring Committee (IDMC) recommended stopping the trial after a planned review found that the experimental regimen was unlikely to demonstrate a benefit in either of the study’s dual primary endpoints: progression-free survival (PFS) or overall survival (OS). The assessment focused on the primary analysis population of patients whose tumors were PD-L1 negative, with expression below 1%.
No new safety signals were identified. AstraZeneca said the safety profile of volrustomig plus chemotherapy remained consistent with the known profiles of the individual treatments.
The drug behind the trial
Volrustomig is a bispecific antibody designed to block two immune checkpoints, PD-1 and CTLA-4, on the same T cell. The rationale is to combine two mechanisms of immune activation in an effort to generate a stronger and more durable anti-tumor response.
The concept is particularly relevant in tumors with low PD-L1 expression, where established PD-1/PD-L1 immunotherapies can deliver less durable responses.
The global, randomized, open-label eVOLVE-Lung02 trial enrolled 895 patients across 25 countries. Patients received either intravenous volrustomig at 750 mg plus chemotherapy or pembrolizumab at 200 mg plus chemotherapy.
A setback within a broader pipeline
The discontinuation is significant because lung cancer is one of the key battlegrounds for AstraZeneca’s oncology business. NSCLC accounts for roughly 80–85% of lung cancers, and many patients are diagnosed only after the disease has metastasized.
For AstraZeneca, however, the volrustomig result is not an isolated development setback. The company has recently faced a series of disappointments across its pipeline, including the late-stage failure of cardiovascular drug Wainua, U.S. regulatory difficulties for breast cancer candidate camizestrant and a trial setback for Ultomiris in a rare disease.
The cumulative setbacks have put additional focus on AstraZeneca’s ability to replenish its pipeline and deliver the growth targets underpinning its long-term strategy. The company continues to target $80 billion in annual revenue by 2030, a goal that depends heavily on successful launches of new medicines.
At the same time, Monday brought positive news from AstraZeneca’s oncology pipeline. Two other late-stage lung cancer studies – involving the Tagrisso/Orpathys combination and Enhertu, developed with Daiichi Sankyo – met their primary endpoints.
What happens next?
AstraZeneca will work with investigators to ensure continued care and follow-up for patients enrolled in eVOLVE-Lung02. The company said other Phase III studies of volrustomig will continue, including trials in cervical cancer, head and neck squamous cell carcinoma and mesothelioma.
For AstraZeneca, the immediate question is therefore not whether volrustomig has failed as a platform, but where its dual-checkpoint approach can deliver a meaningful clinical advantage. The lung cancer result suggests that the strategy has not so far translated into sufficient benefit in this particular first-line setting – raising the stakes for the remaining Phase III program.
Sign up for our newsletter!
