Trial: MEDI5752 in Combination With Carboplati…

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 3

Start date: Nov. 9, 2023

Planned enrollment: 825

Trial ID: NCT06097728

More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: Volrustomig (MEDI5752, PD-1/CTLA-4 DuetMab, MEDI-5752)

Overview

Volrustomig (MEDI5752/MEDI-5752) is an investigational, humanized IgG1 bispecific antibody designed to inhibit both PD-1 and CTLA-4. It is being evaluated alone and in combination regimens across several solid tumors. Early-phase studies have shown antitumor activity, but results vary by tumor type and dose, and efficacy remains unconfirmed in successful randomized phase III trials. (pmc.ncbi.nlm.nih.gov)

In August 2026, the 895-patient phase III eVOLVE-Lung02 trial in first-line metastatic non-small cell lung cancer (NSCLC) was discontinued after an independent monitoring committee concluded that volrustomig plus chemotherapy was unlikely to improve progression-free or overall survival over pembrolizumab plus chemotherapy in the primary PD-L1-negative population. Detailed results have not yet been published. Other phase III studies in cervical cancer, head and neck squamous cell carcinoma (HNSCC), and mesothelioma are continuing. (astrazeneca.com)

Mechanism of action

Volrustomig uses PD-1 binding to concentrate CTLA-4 blockade on activated, PD-1-positive T cells. This design is intended to provide sustained PD-1 inhibition while preferentially inhibiting CTLA-4 on activated rather than resting peripheral T cells, potentially limiting systemic CTLA-4-related toxicity. Pharmacodynamic studies have demonstrated peripheral and intratumoral T-cell proliferation and activation. (aacrjournals.org)

Efficacy

Advanced solid tumors, phase I: Among 86 patients receiving monotherapy across multiple tumor types and doses, the objective response rate (ORR) was 19.8%, including 2.3% complete responses; disease control rate was 53.5%. Median duration of response was 17.5 months, median progression-free survival (PFS) 3.7 months, and median overall survival 19.2 months. The heterogeneous population and nonrandomized design limit interpretation. (doi.org)
First-line advanced clear-cell renal cell carcinoma, phase I expansion: ORRs were 46.9% with 750 mg and 45.5% with 500 mg every three weeks. Complete-response rates were 9.4% and 6.1%, respectively; median PFS was 11.1 and 9.9 months. (annalsofoncology.org)
Recurrent/metastatic HNSCC, phase II interim analysis: Among 19 patients with PD-L1 combined positive score ≥1, five partial responses produced a confirmed ORR of 26.3% and disease-control rate of 52.6%. Follow-up was short at 5.4 months. (ascopubs.org)
Metastatic NSCLC, phase III: eVOLVE-Lung02 was stopped for futility; the regimen was considered unlikely to meet its PFS or overall-survival endpoints versus pembrolizumab plus chemotherapy in patients with PD-L1-negative tumors. Numerical efficacy results have not been released. (astrazeneca.com)

Safety

In the 86-patient phase I monotherapy study, 84.9% experienced treatment-related adverse events (TRAEs), including 38.4% with grade 3–4 events. Common TRAEs included pruritus (30.2%), hypothyroidism (26.7%), hyperthyroidism (24.4%), rash (24.4%), and elevated AST (18.6%). TRAEs caused treatment discontinuation in 33.7%, and one treatment-related death was reported. Hepatic toxicity and discontinuations were more frequent at doses of 1,500 mg or higher, indicating dose-dependent tolerability. (pmc.ncbi.nlm.nih.gov)

In the small HNSCC phase II analysis, grade 3–4 treatment-related events occurred in 8.7% of patients; no patient discontinued because of an adverse event. (ascopubs.org)

TrialFetch AI Analysis

Goal: Determine whether volrustomig plus carboplatin and pemetrexed improves overall survival versus histology-appropriate standard care in advanced unresectable pleural mesothelioma, while assessing safety and other clinical outcomes.

Patients: Adults with histologically confirmed, measurable, advanced unresectable pleural mesothelioma, known epithelioid or non-epithelioid histology, ECOG performance status 0–1, and adequate organ function. Key exclusions include active or prior autoimmune or inflammatory disorders, uncontrolled illness, and untreated or progressive CNS metastases.

Design: Global, multicenter, open-label trial with 1:1 randomization to the investigational regimen or investigator-selected standard care. Comparator options depend on histology.

Treatments: The experimental arm receives volrustomig with carboplatin and pemetrexed. Volrustomig is an investigational bispecific antibody targeting PD-1 and CTLA-4; PD-1 binding is designed to focus CTLA-4 blockade on activated T cells. Early-phase studies across other tumors have shown antitumor activity, but phase III benefit remains unproven; a separate phase III NSCLC trial was stopped for futility. For epithelioid disease, standard care is investigator-selected platinum plus pemetrexed or nivolumab plus ipilimumab; for non-epithelioid disease, it is nivolumab plus ipilimumab.

Outcomes: The primary endpoint is overall survival from randomization. Secondary endpoints include progression-free survival, survival landmarks, response rate and duration, progression after subsequent therapy, patient-reported symptoms and functioning, quality of life, adverse events, volrustomig immunogenicity, and pharmacokinetics, with follow-up for some measures extending to approximately 61 months.

Burden on patient: Moderate to high. Treatment entails repeated clinic visits for intravenous therapy, plus imaging, safety assessments, patient-reported questionnaires, and pharmacokinetic blood sampling over potentially prolonged follow-up. No mandatory research biopsy is specified; the exact visit and sampling schedules are not provided.

Last updated: Sep 2026

Eligibility

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London, Ontario, N6A 5W9, Canada

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Berlin, 14109, Germany

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Bochum, 44791, Germany

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Cologne, 51109, Germany

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Essen, 45122, Germany

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Gauting, 82131, Germany

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Georgsmarienhütte, 49124, Germany

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Großhansdorf, 22927, Germany

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Hamburg, 21075, Germany

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Heidelberg, 69126, Germany

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Kiel, 24105, Germany

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Münster, 48153, Germany

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Regensburg, 93049, Germany

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Berlin, 13125, Germany

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Olsztyn, 10-357, Poland

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Poznan, 60-569, Poland

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Warsaw, 02-781, Poland

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Ulsan, 44033, South Korea

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Seoul, 06591, South Korea

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Seoul, 06351, South Korea

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Oviedo, 33011, Spain

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Barakaldo, 48903, Spain

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Taoyuan District, 333, Taiwan

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Santa Rosa, California, 95403, United States

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Aurora, Colorado, 80045, United States

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Jacksonville, Florida, 32224, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60637, United States

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Baltimore, Maryland, 21231, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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Commack, New York, 11725, United States

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Valhalla, New York, 10595, United States

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Columbus, Ohio, 43210, United States

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Portland, Oregon, 97213, United States

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Portland, Oregon, 97225, United States

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Philadelphia, Pennsylvania, 19104, United States

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Houston, Texas, 77030, United States

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Fairfax, Virginia, 22031, United States

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