AstraZeneca has terminated a late-stage clinical trial for its experimental bispecific antibody volrustomig in metastatic non-small cell lung cancer after an independent monitoring committee concluded the treatment was unlikely to outperform Merck & Co.’s blockbuster immunotherapy Keytruda.
The decision ends the eVOLVE-Lung02 study, which had enrolled 895 participants across 25 countries. The trial evaluated volrustomig combined with chemotherapy as a first-line treatment for patients whose tumors expressed PD-L1 at levels below 50 percent, with the primary analysis focused on those testing negative for the protein.
The Independent Data Monitoring Committee determined during a planned review that the combination was unlikely to meet either of its dual primary endpoints: progression-free survival or overall survival in patients with PD-L1-negative tumors, defined as expression below 1 percent. The comparator arm received Keytruda, known generically as pembrolizumab.
Susan Galbraith, AstraZeneca’s executive vice president of oncology hematology R&D, acknowledged the setback in a statement. “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,” she said. “While we are disappointed, we will learn from this trial and are determined to continue pioneering new medicines from our industry-leading pipeline.”
No unexpected safety signals emerged from the study. The adverse event profile observed with volrustomig plus chemotherapy was consistent with the established safety data for each individual treatment.
Shares of AstraZeneca (AZN) edged higher on the news, climbing roughly 1 percent during the trading session. The muted market reaction reflected what analysts described as a modest recovery following several challenging weeks for the pharmaceutical manufacturer.
A Year of Clinical Setbacks
The volrustomig failure adds to a string of development disappointments for AstraZeneca in 2026. Earlier this year, the company and partner Ionis Pharmaceuticals announced that Wainua failed to outperform placebo in the Phase III CARDIO-TTRansform study, which targeted a progressive and life-threatening cardiac disorder.
Additional setbacks included a U.S. regulatory rejection of the breast cancer therapy camizestrant, with regulators citing trial design deficiencies, and a late-stage disappointment for the rare disease treatment Ultomiris.
While individual clinical failures are an expected component of pharmaceutical development, the cumulative effect has intensified scrutiny on the company’s ability to convert its pipeline investments into commercial successes.
Competing Wins in Lung Cancer
The week nonetheless brought positive news from two other advanced-stage lung cancer programs. AstraZeneca announced favorable results from the DESTINY-Lung04 trial, in which Enhertu — co-developed with Japanese partner Daiichi Sankyo — demonstrated a statistically significant and clinically meaningful improvement in progression-free survival compared with the standard of care in patients with HER2-mutant non-squamous NSCLC.
Enhertu, known generically as trastuzumab deruxtecan, was tested as a first-line treatment against platinum-pemetrexed doublet chemotherapy plus pembrolizumab in patients with unresectable, locally advanced or metastatic disease.
Separately, the Phase III SAFFRON trial showed that combining Tagrisso (osimertinib) with Orpathys (savolitinib) delivered statistically significant improvements in both progression-free survival and overall survival versus doublet platinum-based chemotherapy in patients with EGFR-mutated NSCLC whose tumors exhibited high levels of MET overexpression or amplification and had progressed on prior Tagrisso treatment.
Volrustomig is a bispecific monoclonal antibody designed to simultaneously block two immune checkpoint pathways, PD-1 and CTLA-4, potentially enabling enhanced immune system recognition and destruction of cancer cells. GlobalData analysis projects the drug could reach blockbuster status by 2032 if it succeeds in other indications.
Additional Phase III trials of volrustomig continue as planned in cervical cancer, head and neck squamous cell carcinoma, and mesothelioma.
The Keytruda Shadow
The eVOLVE-Lung02 failure underscores the formidable competitive challenge posed by Keytruda, which has dominated the immuno-oncology market since its approval. The Merck drug was the best-selling medicine globally in 2025, generating $31.7 billion in revenue.
Merck, known as MSD outside the United States and Canada, faces its own looming challenge: global patents protecting Keytruda’s market exclusivity expire in 2028. GlobalData forecasts Keytruda sales will continue growing in the near term, reaching $35.5 billion in 2027, before declining to approximately $19 billion by 2031 as biosimilar competition emerges.
Keytruda accounted for roughly 46 percent of Merck’s total sales in 2024. To offset the impending revenue cliff, the company has outlined plans to launch 20 new products, many with blockbuster potential, according to CEO Robert Davis at the JP Morgan Healthcare Conference in January 2026.
AstraZeneca maintains its own ambitious target of $80 billion in annual revenue by 2030, a goal the company reiterated despite the recent clinical setbacks. The drugmaker exceeded second-quarter earnings projections earlier this year, driven by strong sales in its oncology and rare disease portfolios, and anticipates launching up to 20 novel medications over the coming years.
Axel Rudolph, chief technical analyst at IG, noted that AstraZeneca’s stock has shown recovery indicators, but cautioned that sustained momentum will require positive clinical trial outcomes in the quarters ahead.