eVOLVE-Lung02 Trial of Volrustomig Discontinued in Metastatic NSCLC

AstraZeneca is discontinuing the phase 3 eVOLVE-Lung02 trial (NCT05984277), which evaluated volrustomig plus chemotherapy vs pembrolizumab (Keytruda) plus chemotherapy as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 less than 50%, according to a news release from the company.¹

Why was eVOLVE-Lung02 discontinued?

The decision to discontinue eVOLVE-Lung02 was based on the recommendation of an independent data monitoring committee (IDMC) following a planned review of trial data. The IDMC concluded 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 patients with PD-L1–negative tumors compared with pembrolizumab plus chemotherapy.

The safety profile of volrustomig plus chemotherapy was consistent with the known profiles of the individual medicines, 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 on the trial.

“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,” said Susan Galbraith, executive vice president of Oncology Hematology Research and Development at AstraZeneca, in the press release.¹ “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 was the eVOLVE-Lung02 trial design?

eVOLVE-Lung02 was a randomized, open-label, multicenter, global phase 3 trial that enrolled 895 patients across 25 countries with previously untreated metastatic NSCLC whose tumors express PD-L1 less than 50%. Patients were randomly assigned 1:1 to receive 750 mg of intravenous volrustomig plus chemotherapy every 3 weeks for 4 cycles followed by volrustomig every 3 weeks, or 200 mg of pembrolizumab plus chemotherapy every 3 weeks for 4 cycles followed by pembrolizumab every 3 weeks until completion of 24 months of treatment or disease progression.

The dual primary end points were PFS and OS in patients whose tumors express PD-L1 of less than 1%. Secondary end points included PFS and OS in the intent-to-treat population of patients with PD-L1 of less than 50%, duration of response, overall response rate, and time to deterioration regarding physical functioning.²

Patients 18 years and older with histologically confirmed or cytologically documented squamous or nonsquamous NSCLC, stage IV disease not amenable to curative radiation or surgery, and absence of EGFR mutations and ALK or ROS1 rearrangements were eligible for enrollment on the trial.

Those with mixed small cell lung cancer and NSCLC histology, spinal cord compression, or symptomatic brain metastases were ineligible for study entry. Having a history of another primary malignancy apart from one treated with curative intent with no known active disease for at least 2 years before the first dose of study intervention and of low potential risk for recurrence, adequately treated non-melanoma skin cancer, or adequately treated carcinoma in situ with no evidence of disease were also grounds for exclusion.

What is volrustomig?

Developers engineered volrustomig as a dual checkpoint inhibitor bispecific antibody that delivers coordinated and targeted PD-1 and CTLA-4 blockade on the same T cell. The agent is being assessed as monotherapy and in combinations across several tumor types with high unmet need.

What is next for the volrustomig program?

Although eVOLVE-Lung02 is being discontinued, the other phase 3 volrustomig trials are continuing as planned in cervical cancer, head and neck squamous cell carcinoma, and 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://tinyurl.com/46vtj5y9
2. A global study of volrustomig (MEDI5752) plus chemotherapy versus pembrolizumab plus chemotherapy for participants with metastatic non-small cell lung cancer (eVOLVE-Lung02). ClinicalTrials.gov. Updated July 28, 2026. Accessed August 18, 2026. https://tinyurl.com/4tuca6sk