AstraZeneca is discontinuing the Phase III eVOLVE-Lung02 trial of volrustomig plus chemotherapy after an interim review found it unlikely to meet PFS or OS endpoints in metastatic NSCLC.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
AstraZeneca is discontinuing the Phase III eVOLVE-Lung02 trial (NCT05984277) evaluating volrustomig plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer (mNSCLC) with PD-L1 expression below 50%. The decision follows a planned review by the Independent Data Monitoring Committee (IDMC), which determined that the regimen was unlikely to meet either dual primary endpoint of progression-free survival (PFS) or overall survival (OS) in patients with PD-L1-negative tumors.
Trial Fails to Support Volrustomig in PD-L1-Negative Disease
eVOLVE-Lung02 was designed to compare volrustomig plus chemotherapy with pembrolizumab plus chemotherapy in patients whose tumors expressed PD-L1 below 50%. The primary analysis population comprised patients with PD-L1 expression below 1%, a group with limited response to current immunotherapy approaches.
The IDMC concluded that volrustomig plus chemotherapy was unlikely to demonstrate a clinically meaningful benefit in either PFS or OS versus the pembrolizumab-based comparator. AstraZeneca will therefore discontinue the trial rather than continue enrollment or treatment under the existing study design.
No new safety signals emerged. The safety profile of volrustomig combined with chemotherapy remained consistent with the established safety profiles of the individual medicines.
895 Patients Enrolled Across 25 Countries
eVOLVE-Lung02 was a randomized, open-label, multicenter global Phase III study involving 895 patients across 25 countries. Participants were randomized 1:1 to receive either volrustomig or pembrolizumab, each combined with chemotherapy.
Patients in the experimental arm received 750 mg of intravenous volrustomig every three weeks for four chemotherapy cycles, followed by volrustomig every three weeks. The comparator arm received 200 mg of pembrolizumab every three weeks with chemotherapy for four cycles, followed by pembrolizumab every three weeks.
Treatment continued until disease progression, completion of 24 months of therapy, or another discontinuation criterion.
The dual primary endpoints were PFS and OS in patients with PD-L1 expression below 1%. Secondary endpoints included PFS and OS in the broader intent-to-treat population with PD-L1 expression below 50%.
Volrustomig Targets PD-1 and CTLA-4
Volrustomig is a bispecific antibody that simultaneously targets PD-1 and CTLA-4 on the same T cell. The approach is intended to combine two immune checkpoint blockade mechanisms within a single molecule and potentially enhance antitumor immune activity.
The setback in eVOLVE-Lung02 comes in a disease setting where immunotherapy has become central to first-line treatment, but outcomes remain less durable for some patients with low or absent PD-L1 expression.
Lung cancer remains the leading cause of cancer mortality worldwide. NSCLC accounts for approximately 80% to 85% of lung cancer cases, and many patients present with metastatic disease. The five-year survival rate for metastatic NSCLC remains approximately 12%.
Other Volrustomig Trials Continue
Susan Galbraith, Executive Vice President of Oncology Haematology R&D at AstraZeneca, said the company was disappointed by the result but would use the findings to inform continued development of its oncology pipeline.
The company will work with investigators to maintain continuity of care and appropriate follow-up for patients enrolled in eVOLVE-Lung02.
The discontinuation does not affect other Phase III volrustomig programs. Trials evaluating the bispecific antibody in cervical cancer, head and neck squamous cell carcinoma, and mesothelioma will continue as planned.
The eVOLVE-Lung02 outcome therefore represents a setback for volrustomig in first-line PD-L1-low metastatic NSCLC, while AstraZeneca continues to assess whether its dual PD-1/CTLA-4 strategy can demonstrate benefit in other tumor types and clinical settings.
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About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.