AstraZeneca is discontinuing the phase 3 eVOLVE-Lung02 trial evaluating volrustomig plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express programmed cell death ligand 1 (PD-L1) below 50%, the company announced August 17, 2026.¹
The decision follows a recommendation from an independent data monitoring committee (IDMC) after a planned review of trial data determined that the combination was unlikely to meet either of the trial's dual primary endpoints, which are progression-free survival (PFS) or overall survival (OS), in the primary analysis population of patients with PD-L1–negative tumors (below 1%), compared with pembrolizumab plus chemotherapy.¹
Key facts
- Drug: Volrustomig (AstraZeneca)
- Class: PD-1/CTLA-4 bispecific antibody; dual checkpoint inhibitor
- Indication studied: 1L metastatic NSCLC, PD-L1 <50% (primary analysis PD-L1 <1%)
- Trial: eVOLVE-Lung02 (phase 3); 895 patients across 25 countries
- Comparator: Pembrolizumab plus chemotherapy
- Status: Discontinued August 17, 2026, on IDMC recommendation
- Reason: Unlikely to meet dual primary endpoints of PFS/OS
- Safety: Consistent with known profiles; no new signals identified
- Pipeline context: Volrustomig phase 3 trials continue in cervical, head and neck, and mesothelioma cancers
- Same-day news: Enhertu (trastuzumab deruxtecan) met its PFS endpoint in DESTINY-Lung04 for HER2-mutant NSCLC
“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, PhD, executive vice president, oncology hematology R&D, AstraZeneca, in a company press release.1 “While we are disappointed, we will learn from this trial and are determined to continue pioneering new medicines from our … pipeline in our quest to improve outcomes for patients with lung cancer.”
Why was the eVOLVE-Lung02 trial testing volrustomig in lower PD-L1 NSCLC?
Lung cancer is the leading cause of cancer death worldwide, causing nearly 1 in 4 cancer deaths, and NSCLC accounts for 80% to 85% of cases. Only about 12% of patients with metastatic NSCLC survive 5 years.³ Patients with lower PD-L1 expression typically see less durable responses to existing immunotherapy, the gap eVOLVE-Lung02 was designed to address.¹
eVOLVE-Lung02 was a randomized, open-label, global trial enrolling 895 patients across 25 countries. Patients received 750 mg volrustomig plus chemotherapy or 200 mg pembrolizumab plus chemotherapy every 3 weeks for 4 cycles, followed by the respective monotherapy for up to 24 months or until progression. Dual primary endpoints were PFS and OS in patients with PD-L1 below 1%, and secondary endpoints covered the broader PD-L1 below 50% population.¹
How does volrustomig work, and why did the trial fail to meet its endpoints?
Volrustomig is a bispecific antibody designed to block both programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the same T cell, an approach intended to deliver more coordinated immune activation than blocking either checkpoint alone. Its safety profile alongside chemotherapy was consistent with the known profiles of the individual medicines, with no new signals identified. AstraZeneca said it will work with investigators to ensure continuity of care for patients already enrolled.¹
What other milestones has AstraZeneca's lung cancer pipeline achieved?
The eVOLVE-Lung02 discontinuation does not affect the rest of AstraZeneca's volrustomig program, which include phase 3 trials in cervical cancer, head and neck squamous cell carcinoma, and mesothelioma continue as planned, and the antibody is also being evaluated as monotherapy and in other combinations across additional tumor types with high unmet need.¹
The update was announced the same day AstraZeneca and partner Daiichi Sankyo reported positive DESTINY-Lung04 data, a global phase 3 trial of 454 patients that showed trastuzumab deruxtecan (Enhertu) met its primary endpoint as first-line treatment for advanced HER2-mutant non-squamous NSCLC, with a statistically significant, clinically meaningful PFS improvement versus standard-of-care platinum-pemetrexed chemotherapy plus pembrolizumab. The study represents the first phase 3 trial to beat that standard in this setting, according to Dr Galbraith.² HER2 mutations occur in roughly 2% to 4% of non-squamous NSCLC cases and predominantly affect younger patients and never-smokers, a population with poorer prognosis and more brain metastases.²
What are the limitations?
AstraZeneca's has not released the underlying PFS or OS data behind the IDMC's recommendation, so the magnitude of difference between arms remains unknown. Neither the eVOLVE-Lung02 nor the same-day DESTINY-Lung04 results have to date been presented at a medical meeting or published in a manuscript.
References
- AstraZeneca. Update on eVOLVE-Lung02 phase 3 trial of volrustomig plus chemotherapy in metastatic non-small cell lung cancer. Press release. Published August 17, 2026. Accessed August 17, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/update-on-evolve-lung02-phase-iii-trial.html
- AstraZeneca. Enhertu demonstrated statistically significant and clinically meaningful improvement in progression-free survival as first-line treatment of patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 phase 3 trial. Press release. Published August 17, 2026. Accessed August 17, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/enhertu-improved-pfs-in-1l-her2m-lung-cancer.html
- World Health Organization International Agency for Research on Cancer. Trachea, bronchus and lung fact sheet. Globocan 2024. Accessed August 17, 2026. https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf
- American Cancer Society. Lung cancer survival rates. Accessed August 17, 2026. https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/survival-rates.html
