Phase 3 eVOLVE-Lung02 Trial of First-Line Volrustomig Is Discontinued in First-Line Metastatic NSCLC

AstraZeneca is discontinuing the phase 3 eVOLVE-Lung02 trial (NCT05984277) evaluating volrustomig (MEDI5752) plus chemotherapy vs pembrolizumab (Keytruda) plus chemotherapy as a first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 at less than 50%.¹

The decision was based on a recommendation from the trial's independent data monitoring committee (IDMC), which concluded following a planned review of trial data that the volrustomig combination was unlikely to meet either of the dual primary end points of progression-free survival (PFS) or overall survival (OS) in the primary analysis population of patients with PD-L1–negative tumors (<1%) vs the comparator arm.

The safety profile of volrustomig plus chemotherapy was consistent with the known profiles of the individual agents, and no new safety signals were identified. The company said it will work with investigators to ensure continuity of care and appropriate follow-up for patients enrolled in the trial. Detailed data from eVOLVE-Lung02 were not reported in the release.

“We initiated the eVOLVE-Lung02 trial aiming to improve the outcomes for patients whose lung cancers have lower PD-L1 expression and a less durable response to current immunotherapy regimens,” Susan Galbraith, executive vice president of Oncology Hematology R&D at AstraZeneca, stated in a news release. “While we are disappointed, we will learn from this trial and are determined to continue pioneering new medicines from our industry-leading pipeline in our quest to improve outcomes for patients with lung cancer.”

What is the mechanism of action of volrustomig?

Volrustomig is a dual–checkpoint inhibitor bispecific antibody designed to deliver coordinated and targeted PD-1 and CTLA-4 blockade on the same T cell. The company is evaluating the agent as monotherapy and in combination regimens across several tumor types with high unmet need.

How was the eVOLVE-Lung02 trial designed?

eVOLVE-Lung02 was a randomized, open-label, multicenter, global phase 3 trial evaluating volrustomig plus chemotherapy for the first-line treatment of patients with metastatic NSCLC whose tumors express PD-L1 at less than 50%.^1,2 The trial enrolled 895 patients across 25 countries.¹

To be eligible, patients were required to have histologically or cytologically documented stage IV squamous or nonsquamous NSCLC without sensitizing EGFR mutations or ALK or ROS1 rearrangements.² Patients with mixed small cell lung cancer and NSCLC histology or sarcomatoid variants were excluded; Symptomatic brain metastases also precluded patients from participation.

Patients were randomly assigned 1:1 to receive 750 mg of intravenous volrustomig plus chemotherapy every 3 weeks for four cycles, followed by volrustomig every 3 weeks; or 200 mg of pembrolizumab plus chemotherapy every 3 weeks for four cycles, followed by pembrolizumab every 3 weeks until the completion of 24 months of treatment, disease progression, or another discontinuation criterion was met.¹

The dual primary end points were PFS and OS in patients whose tumors express PD-L1 at less than 1%. Secondary end points included PFS and OS in the intent-to-treat population (PD-L1 <50%), as well as overall response rate, duration of response, and time to second progression.²

What are the next steps for volrustomig?

Volrustomig continues to be evaluated in other phase 3 trials, which are proceeding as planned.¹ These include the phase 3 eVOLVE-Cervical trial (NCT06079671) in patients wtih high-risk locally advanced cervical cancer, the phase 3 eVOLVE-HNSCC trial (NCT06129864) in patients with unresected locally advanced head and neck squamous cell carcinoma, and the phase 3 eVOLVE-Meso trial (NCT06097728) in patients with unresectable pleural mesothelioma.

References

1. Update on eVOLVE-Lung02 Phase III trial of volrustomig plus chemotherapy in metastatic non-small cell lung cancer. News release. AstraZeneca. August 17, 2026. Accessed August 17, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/update-on-evolve-lung02-phase-iii-trial.html
2. A global study of volrustomig (MEDI5752) plus chemotherapy versus pembrolizumab plus chemotherapy for participants with metastatic non-small cell lung cancer. ClinicalTrials.gov. Updated July 28, 2026. Accessed August 17, 2026. https://clinicaltrials.gov/study/NCT05984277