AstraZeneca has ended a Phase III trial of its bispecific volrustomig pitted against MSD’s blockbuster Keytruda (pembrolizumab) in non-small cell lung cancer (NSCLC) after it was deemed unlikely to show superiority.
The Independent Data Monitoring Committee (IDMC) looked over data from the eVOLVE-Lung02 study (NCT05984277) of volrustomig during a planned review.
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Their analysis found that volrustomig in combination with chemotherapy was unlikely to meet either of the dual primary endpoints of progression-free survival (PFS) or overall survival (OS) in the primary analysis population of patients with PD-L1-negative tumours (<1%) versus the Keytruda comparator arm.
The study pitted the two regimens against each other as a first-line therapy in patients with metastatic NSCLC whose tumours express PD-L1 <50%.
The safety profile of volrustomig plus chemotherapy was consistent with the known profiles of the individual medicines and no new safety signals were identified.
Susan Galbraith, executive vice president of oncology haematology R&D at AstraZeneca, said: “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. 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.”
Other Phase III volrustomig trials continue as planned in cervical cancer, head and neck squamous cell carcinoma and mesothelioma.
Volrustomig is a dual checkpoint inhibitor bispecific monoclonal antibody (mAb) designed to unblock two key immune pathways, PD-1 and CTLA-4. GlobalData analysis predicts the drug will hit blockbuster status in 2032.
GlobalData is the parent company of Clinical Trials Arena.
Two wins and a loss for AZ in NSCLC
Despite the trial termination, AstraZeneca did share two NSCLC wins at the same time, sending the company’s share price up very slightly.
In the DESTINY-Lung04 Phase III trial (NCT05048797), Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus the global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as first-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous NSCLC.
Also, in the Phase III SAFFRON trial (NCT05261399), Tagrisso (osimertinib) plus Orpathys (savolitinib) demonstrated a statistically significant and clinically meaningful improvement in both PFS and OS versus doublet platinum-based chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) NSCLC. Patients in the trial had tumours with high levels of MET overexpression or amplification and had progressed on prior treatment with Tagrisso.
MSD seeking to fill Keytruda finance hole
Meanwhile, MSD is hoping to find its own drug that can succeed Keytruda, given its flagship blockbuster is set to lose exclusivity. Keytruda was the best-selling drug on the market in 2025 after bringing in $31.7bn for the company.
While GlobalData forecasts that Keytruda sales will continue to grow for the next couple of years – making $35.5bn for the company in 2027 – global patents covering the drug’s market exclusivity are set to expire in 2028. This will likely result in significant losses for MSD, as Keytruda accounted for around 46% of the company’s sales in 2024. GlobalData predicts sales of the drug in 2031 to drop to $19bn.
To offset this impact, MSD has devised a strategy to add further value to its marketed portfolio, with the company expecting the launch of 20 new products, many of which have blockbuster potential, said CEO Robert Davis at the JP Morgan Conference 2026 in January.
