Volrustomig (MEDI5752) Phase 3 Trial in Pleural Mesothelioma (NCT06097728)

What the Trial Is Testing

NCT06097728 is a global Phase 3 study sponsored by AstraZeneca testing whether volrustomig (MEDI5752), an investigational bispecific antibody, plus carboplatin and pemetrexed chemotherapy can improve outcomes for adults newly diagnosed with unresectable pleural mesothelioma. The experimental arm is volrustomig + carboplatin + pemetrexed. The comparator arm uses the investigator’s choice of either platinum (carboplatin or cisplatin) plus pemetrexed alone, or nivolumab plus ipilimumab, which is one of the two FDA-approved first-line regimens. Randomization is open-label with stratification by histology and other factors per the published protocol on ClinicalTrials.gov.

The trial reflects the current first-line treatment landscape in pleural mesothelioma. Two FDA-approved regimens already exist: nivolumab plus ipilimumab (Baas et al., Lancet 2021; Scherpereel et al., JCO 2026 5-year update) and pembrolizumab plus pemetrexed and platinum (Chu et al., Lancet 2024; FDA approval September 17, 2024). NCT06097728 asks whether a single bispecific antibody combined with platinum-pemetrexed produces durable responses competitive with those benchmarks.

How Volrustomig Differs from Nivolumab Plus Ipilimumab

Volrustomig is a bispecific antibody. A single molecule binds both PD-1 and CTLA-4. The clinical theory underlying bispecifics is that targeting both checkpoints with one molecule may produce more T-cell activation than two separate antibodies given together, while potentially shifting the toxicity profile because the binding affinities for PD-1 and CTLA-4 can be tuned separately. Whether that theory translates into improved outcomes for pleural mesothelioma is exactly the question the Phase 3 trial is designed to answer.

The nivolumab plus ipilimumab comparator arm in this trial is the FDA-approved first-line regimen from CheckMate-743. Patients randomized to that arm receive the standard-of-care treatment. The platinum-pemetrexed comparator was the standard before immunotherapy approvals and remains one of the investigator’s choices in the protocol. By including both as comparators, the trial allows AstraZeneca to demonstrate volrustomig’s effect against the most relevant clinical alternatives.

Trial Design Details

How This Fits the Mesothelioma Treatment Landscape

The Phase 3 design tests volrustomig against the strongest current standard. CheckMate-743 reported a 5-year overall survival of 14% on nivolumab plus ipilimumab versus 6% on chemotherapy alone (Scherpereel et al., Journal of Clinical Oncology 2026). KEYNOTE-483 / IND-227 showed pembrolizumab plus pemetrexed and platinum was non-inferior on overall survival to platinum-pemetrexed alone, with the FDA approving the regimen as a second first-line option in 2024.

For volrustomig to change practice, it needs to demonstrate either a statistically meaningful overall survival benefit over both comparator arms or a clinically relevant improvement in tolerability. The trial is open-label and powered for survival endpoints. The full protocol, including primary and secondary endpoints, is on the ClinicalTrials.gov record.

For people considering trial enrollment generally, the clinical trial enrollment guide walks through how to read a trial listing, decode eligibility criteria, and contact a study coordinator.

Study Locations

Recruitment is open at sites in multiple U.S. states and in countries across Europe, Asia, and the Pacific per ClinicalTrials.gov. U.S. locations include Arizona, California, Colorado, Florida, and others. The full site list is maintained on the ClinicalTrials.gov record and is updated as new sites activate.