A Phase III, Randomized, Open-Label, Multicenter, Global Study of Volrustomig (MEDI5752) in Combination With Carboplatin Plus Pemetrexed Versus Platinum Plus Pemetrexed or Nivolumab Plus Ipilimumab in Participants With Unresectable Pleural Mesothelioma (eVOLVE-Meso)

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 3

Start date: Nov. 9, 2023

Planned enrollment: 825

Trial ID: NCT06097728
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

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

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Goal: Assess whether volrustomig (MEDI5752) combined with carboplatin and pemetrexed improves overall survival versus current standard first-line options in unresectable pleural mesothelioma.

Patients: Adults (≥18 years) with histologically confirmed unresectable pleural mesothelioma (epithelioid or non-epithelioid), measurable disease by modified RECIST 1.1, ECOG 0–1, and adequate organ function. Key exclusions include active or prior significant autoimmune/inflammatory disease, uncontrolled infections (including uncontrolled HBV/HCV/HIV, tuberculosis), uncontrolled intercurrent illness, untreated or progressive CNS metastases, and concurrent anticancer therapy.

Design: Global, multicenter, phase III, randomized (1:1), open-label, active-controlled study. Patients are stratified by histology, with investigator’s choice comparator aligned to histologic subtype. Planned enrollment is 825 participants.

Treatments: Experimental: volrustomig plus carboplatin and pemetrexed. Volrustomig (MEDI5752) is a monovalent bispecific antibody targeting PD-1 and CTLA-4, designed to fully inhibit PD-1 and preferentially inhibit CTLA-4 on activated PD-1–positive T cells within tumors, potentially enhancing intratumoral immune activation while reducing peripheral toxicity compared with separate PD-1 and CTLA-4 antibodies. The bispecific format promotes PD-1 internalization and degradation, which may differentiate pharmacodynamics from conventional combinations. Early-phase studies in solid tumors, including first-line renal cell carcinoma, have shown encouraging activity with objective response rates around 45–48% at 500–750 mg every 3 weeks, with dose-dependent immune-related toxicity escalating at doses ≥1500 mg; current development focuses on lower doses to optimize benefit-risk. Comparator: investigator’s choice of platinum (cisplatin or carboplatin) plus pemetrexed for epithelioid histology or nivolumab plus ipilimumab for either epithelioid or non-epithelioid histology; for non-epithelioid histology, nivolumab plus ipilimumab is the specified standard regimen.

Outcomes: Primary endpoint: overall survival comparing the experimental versus comparator arm. Key secondary endpoints include overall survival (descriptive), progression-free survival per mRECIST 1.1/RECIST 1.1, landmark OS (12, 18, 24, 36 months) and PFS (6, 12, 18, 24 months), overall response rate, duration of response, PFS2, patient-reported outcomes (physical function via PROMIS PF 8c; disease-related symptoms via EORTC IL305 and PRO-CTCAE; role functioning via EORTC QLQ-C30 RF; global HRQoL via EORTC QLQ-C30), immunogenicity of volrustomig (anti-drug antibodies), safety (CTCAE v5.0), and volrustomig pharmacokinetics (AUC, Cmax, Tmax).

Burden on patient: Moderate. As a phase III study with intravenous therapy, patients will undergo regular clinic visits for infusions, routine labs, and radiographic assessments per mRECIST/RECIST schedules typical for mesothelioma (approximately every 6–12 weeks). Additional burden arises from pharmacokinetic sampling and immunogenicity assessments for volrustomig, which require extra blood draws at specified time points, and comprehensive safety monitoring for immune-related adverse events. There are no mandated research biopsies described, and the comparator regimens and imaging frequency align with standard care, keeping overall burden below that of intensive early-phase trials but higher than usual care due to PK/ADA sampling and detailed PRO collection across approximately 5 years of follow-up.

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Kitaadachi-gun, 362-0806, Japan

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Polokwane, 0700, South Africa

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Cape Town, 7570, South Africa

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Johannesburg, 2013, South Africa

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Ulsan, 44033, South Korea

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Kaohsiung City, 80756, Taiwan

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Phoenix, Arizona, 85054, United States

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Commack, New York, 11725, United States

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Cleveland, Ohio, 44124, United States

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Columbus, Ohio, 43210, United States

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Portland, Oregon, 97239, United States

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Portland, Oregon, 97225, United States

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Portland, Oregon, 97213, 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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