Sponsor: AstraZeneca (industry)
Phase: 3
Start date: Nov. 9, 2023
Planned enrollment: 825
Volrustomig, also known as MEDI5752 or PD-1/CTLA-4 DuetMab, is an investigational bispecific monoclonal antibody targeting both PD-1 and CTLA-4 immune checkpoints. It is designed to fully inhibit PD-1 while preferentially inhibiting CTLA-4 on activated PD-1–positive T cells, aiming to enhance antitumor immune responses. (oncologypro.esmo.org)
Volrustomig's bispecific nature allows it to simultaneously block PD-1 and CTLA-4 pathways. This dual inhibition is intended to restore and amplify T-cell activity against tumor cells, potentially leading to improved therapeutic outcomes compared to targeting either checkpoint alone. (aacrjournals.org)
In a Phase 1 study involving treatment-naïve patients with advanced clear cell renal cell carcinoma (ccRCC), volrustomig demonstrated promising efficacy:
Median progression-free survival (PFS): 12.3 months
500 mg dose cohort (V500):
These results suggest that volrustomig has the potential to improve outcomes in patients with advanced RCC. (onclive.com)
The safety profile of volrustomig is consistent with dual checkpoint inhibition:
46.9% of patients discontinued treatment due to TRAEs.
500 mg dose cohort (V500):
One treatment-related death occurred in the V500 cohort due to bronchopulmonary aspergillosis with immune neutropenia. (onclive.com)
Last updated: Apr 2025
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.
Key Inclusion Criteria:
* Participant must be ≥ 18 years at the time of screening
* Histologically proven diagnosis of pleural mesothelioma with known histology (epithelioid vs. non-epithelioid)
* Advanced unresectable disease that cannot be treated with curative surgery (with or without chemotherapy)
* WHO/ECOG performance status of 0 or 1 with no deterioration (that is, ECOG PS\>1) over the previous 2 weeks prior to day of first dosing
* Has measurable disease per modified RECIST1.1
* Has adequate bone marrow reserve and organ function at baseline
Key Exclusion Criteria:
* As judged by the investigator, any condition that would interfere with evaluation of the investigational product or interpretation of participant safety or study results.
* Active or prior documented autoimmune or inflammatory disorders
* History of another primary malignancy with exceptions.
* Uncontrolled intercurrent illness
* Tuberculosis, hepatitis B (HBV) or hepatitis C (HCV), human immunodeficiency virus (HIV) infection that is not well controlled
* Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment
* Untreated or progressive CNS metastatic disease
Chermside, 4032, Australia
No email / No phone
Status: Recruiting
Westmead, 2145, Australia
No email / No phone
Status: Recruiting
Nedlands, 6009, Australia
No email / No phone
Status: Recruiting
Melbourne, 3000, Australia
No email / No phone
Status: Recruiting
Clayton, 3168, Australia
No email / No phone
Status: Recruiting
Ghent, 9000, Belgium
No email / No phone
Status: Recruiting
Leuven, 3000, Belgium
No email / No phone
Status: Withdrawn
Sint-Niklaas, 9100, Belgium
No email / No phone
Status: Recruiting
Hasselt, 3500, Belgium
No email / No phone
Status: Recruiting
Anderlecht, 1070, Belgium
No email / No phone
Status: Recruiting
Antwerp, 2020, Belgium
No email / No phone
Status: Recruiting
Porto Alegre, 91350-200, Brazil
No email / No phone
Status: Recruiting
Rio de Janeiro, 22281-100, Brazil
No email / No phone
Status: Recruiting
São Paulo, 01246-000, Brazil
No email / No phone
Status: Recruiting
Santo André, 09060-650, Brazil
No email / No phone
Status: Recruiting
Barretos, 14784-400, Brazil
No email / No phone
Status: Recruiting
Fortaleza, 60336-045, Brazil
No email / No phone
Status: Recruiting
João Pessoa, 58013-140, Brazil
No email / No phone
Status: SUSPENDED
Edmonton, Alberta, T6G 1Z2, Canada
No email / No phone
Status: Recruiting
Hamilton, Ontario, L8V 1C3, Canada
No email / No phone
Status: Withdrawn
London, Ontario, N6A 5W9, Canada
No email / No phone
Status: Recruiting
Ottawa, Ontario, K1H 8L6, Canada
No email / No phone
Status: Recruiting
Toronto, Ontario, M5G 1X6, Canada
No email / No phone
Status: Recruiting
Montreal, Quebec, H2X 0C1, Canada
No email / No phone
Status: Recruiting
Québec, Quebec, G1V 4G5, Canada
No email / No phone
Status: Recruiting
Shandong, China
No email / No phone
Status: Recruiting
Zhengzhou, 450052, China
No email / No phone
Status: Not yet recruiting
Zhengzhou, 450008, China
No email / No phone
Status: Recruiting
Xi'an, 710061, China
No email / No phone
Status: Recruiting
Wuhan, 430030, China
No email / No phone
Status: Recruiting
Tianjin, 300060, China
No email / No phone
Status: Recruiting
Tianjin, 300050, China
No email / No phone
Status: Recruiting
Taiyuan, 030032, China
No email / No phone
Status: Recruiting
Taiyuan, 030000, China
No email / No phone
Status: Recruiting
Shenyang, 110044, China
No email / No phone
Status: Recruiting
Changsha, 410013, China
No email / No phone
Status: Recruiting
Chengdu, 610042, China
No email / No phone
Status: Recruiting
Chongqing, 400030, China
No email / No phone
Status: Recruiting
Guangzhou, 510060, China
No email / No phone
Status: Withdrawn
Guangzhou, 510100, China
No email / No phone
Status: Recruiting
Guangzhou, 510180, China
No email / No phone
Status: Withdrawn
Hangzhou, 310022, China
No email / No phone
Status: Recruiting
Harbin, 150049, China
No email / No phone
Status: Recruiting
Kunming, 650118, China
No email / No phone
Status: Recruiting
Lanzhou, 730000, China
No email / No phone
Status: Recruiting
Nanchang, 330006, China
No email / No phone
Status: Withdrawn
Ningbo, 315100, China
No email / No phone
Status: Recruiting
Qingdao, 266003, China
No email / No phone
Status: Not yet recruiting
Shanghai, 200032, China
No email / No phone
Status: Recruiting
Beijing, 100142, China
No email / No phone
Status: Recruiting
Beijing, 100210, China
No email / No phone
Status: Not yet recruiting
Changchun, 130021, China
No email / No phone
Status: Not yet recruiting
Aarhus N, 8200, Denmark
No email / No phone
Status: Recruiting
Copenhagen, 2100, Denmark
No email / No phone
Status: Recruiting
Brest, 29200, France
No email / No phone
Status: Recruiting
Créteil, 94010, France
No email / No phone
Status: Recruiting
Le Mans, 72037, France
No email / No phone
Status: Recruiting
Lille, 59037, France
No email / No phone
Status: Recruiting
Lyon, 69373, France
No email / No phone
Status: Recruiting
Marseille, 13015, France
No email / No phone
Status: Recruiting
Montpellier, 34298, France
No email / No phone
Status: Recruiting
Paris, 75877, France
No email / No phone
Status: Recruiting
Rouen, 76031, France
No email / No phone
Status: Recruiting
Saint-Herblain, 44800, France
No email / No phone
Status: Recruiting
Strasbourg, 67091, France
No email / No phone
Status: Recruiting
Toulouse, 31059, France
No email / No phone
Status: Recruiting
Berlin, 13125, Germany
No email / No phone
Status: Recruiting
Berlin, 14109, Germany
No email / No phone
Status: Recruiting
Bochum, 44791, Germany
No email / No phone
Status: Recruiting
Cologne, 51109, Germany
No email / No phone
Status: Recruiting
Essen, 45122, Germany
No email / No phone
Status: Not yet recruiting
Essen, 45130, Germany
No email / No phone
Status: Withdrawn
Gauting, 82131, Germany
No email / No phone
Status: Recruiting
Georgsmarienhütte, 49124, Germany
No email / No phone
Status: Recruiting
Großhansdorf, 22927, Germany
No email / No phone
Status: Recruiting
Hamburg, 21075, Germany
No email / No phone
Status: Recruiting
Heidelberg, 69126, Germany
No email / No phone
Status: Recruiting
Kiel, 24105, Germany
No email / No phone
Status: Recruiting
Münster, 48153, Germany
No email / No phone
Status: Recruiting
Regensburg, 93049, Germany
No email / No phone
Status: Recruiting
Milan, 20141, Italy
No email / No phone
Status: Recruiting
Varese, 21100, Italy
No email / No phone
Status: Recruiting
Rozzano, 20089, Italy
No email / No phone
Status: Recruiting
Parma, 43100, Italy
No email / No phone
Status: Recruiting
Padua, 35128, Italy
No email / No phone
Status: Recruiting
Orbassano, 10043, Italy
No email / No phone
Status: Recruiting
Monza, 20052, Italy
No email / No phone
Status: Recruiting
Alessandria, 15100, Italy
No email / No phone
Status: Recruiting
Bari, 70124, Italy
No email / No phone
Status: Recruiting
Bergamo, 24125, Italy
No email / No phone
Status: Recruiting
Nishinomiya-shi, 663-8501, Japan
No email / No phone
Status: Recruiting
Nagoya, 466-8560, Japan
No email / No phone
Status: Recruiting
Matsuyama, 791-0280, Japan
No email / No phone
Status: Recruiting
Kitakyushu-shi, 807-8555, Japan
No email / No phone
Status: Recruiting
Kitaadachi-gun, 362-0806, Japan
No email / No phone
Status: Not yet recruiting
Hiroshima, 734-8551, Japan
No email / No phone
Status: Recruiting
Hakodate-shi, 040-8611, Japan
No email / No phone
Status: Recruiting
Amagasaki-shi, 660-8550, Japan
No email / No phone
Status: Recruiting
Ube-shi, 755-0241, Japan
No email / No phone
Status: Recruiting
Tokyo, 104-0045, Japan
No email / No phone
Status: Recruiting
Osakasayama-shi, 589-8511, Japan
No email / No phone
Status: Recruiting
Okayama, 702-8055, Japan
No email / No phone
Status: Recruiting
Amsterdam, 1066CX, Netherlands
No email / No phone
Status: Recruiting
Rotterdam, 3015 GD, Netherlands
No email / No phone
Status: Recruiting
Eindhoven, 5623EJ, Netherlands
No email / No phone
Status: Recruiting
Oslo, 450, Norway
No email / No phone
Status: Recruiting
Lørenskog, 1478, Norway
No email / No phone
Status: Recruiting
Bystra, 43-360, Poland
No email / No phone
Status: Recruiting
Bydgoszcz, 85-796, Poland
No email / No phone
Status: Withdrawn
Olsztyn, 10-357, Poland
No email / No phone
Status: Recruiting
Poznan, 60-569, Poland
No email / No phone
Status: Recruiting
Rzeszów, 35-241, Poland
No email / No phone
Status: Withdrawn
Warsaw, 02-781, Poland
No email / No phone
Status: Recruiting
Johannesburg, 2193, South Africa
No email / No phone
Status: Recruiting
eManzimtoti, 4126, South Africa
No email / No phone
Status: Recruiting
Kimberly, 8301, South Africa
No email / No phone
Status: Recruiting
Pretoria, 0081, South Africa
No email / No phone
Status: Recruiting
Pretoria, 0002, South Africa
No email / No phone
Status: Recruiting
Polokwane, 0700, South Africa
No email / No phone
Status: Withdrawn
Cape Town, 7570, South Africa
No email / No phone
Status: Recruiting
Johannesburg, 2013, South Africa
No email / No phone
Status: SUSPENDED
Seoul, 06351, South Korea
No email / No phone
Status: Recruiting
Seoul, 06591, South Korea
No email / No phone
Status: Recruiting
Ulsan, 44033, South Korea
No email / No phone
Status: Not yet recruiting
Cheongju-si, 28644, South Korea
No email / No phone
Status: Withdrawn
Seoul, 03080, South Korea
No email / No phone
Status: Recruiting
Madrid, 28041, Spain
No email / No phone
Status: Recruiting
Barcelona, 8035, Spain
No email / No phone
Status: Recruiting
Barakaldo, 48903, Spain
No email / No phone
Status: Recruiting
Oviedo, 33011, Spain
No email / No phone
Status: Recruiting
Sankt Gallen, 9007, Switzerland
No email / No phone
Status: Recruiting
Basel, 4031, Switzerland
No email / No phone
Status: Recruiting
Baden, CH-5405, Switzerland
No email / No phone
Status: Recruiting
Bern, 3010, Switzerland
No email / No phone
Status: Recruiting
Fribourg, 1700, Switzerland
No email / No phone
Status: Recruiting
Taoyuan District, 333, Taiwan
No email / No phone
Status: Not yet recruiting
Taichung, 40705, Taiwan
No email / No phone
Status: Recruiting
Tainan City, 70403, Taiwan
No email / No phone
Status: Recruiting
Taipei, 10002, Taiwan
No email / No phone
Status: Recruiting
Kaohsiung City, 80756, Taiwan
No email / No phone
Status: Recruiting
Izmir, 35110, Turkey (Türkiye)
No email / No phone
Status: Recruiting
Diyarbakır, 21280, Turkey (Türkiye)
No email / No phone
Status: Recruiting
Adana, 01060, Turkey (Türkiye)
No email / No phone
Status: Withdrawn
Ankara, 06280, Turkey (Türkiye)
No email / No phone
Status: SUSPENDED
Ankara, 06800, Turkey (Türkiye)
No email / No phone
Status: Recruiting
Manchester, M23 9LT, United Kingdom
No email / No phone
Status: Recruiting
London, SW3 6JJ, United Kingdom
No email / No phone
Status: Recruiting
London, SE1 9RT, United Kingdom
No email / No phone
Status: Recruiting
London, NW1 2PG, United Kingdom
No email / No phone
Status: Recruiting
Leicester, LE1 5WW, United Kingdom
No email / No phone
Status: Recruiting
Leeds, LS9 7TF, United Kingdom
No email / No phone
Status: Recruiting
Cardiff, Wales, CF5 6NF, United Kingdom
No email / No phone
Status: Withdrawn
Cambridge, CB20QQ, United Kingdom
No email / No phone
Status: Recruiting
Taunton, TA1 5DA, United Kingdom
No email / No phone
Status: Recruiting
Portsmouth, PO6 3LY, United Kingdom
No email / No phone
Status: Recruiting
Newcastle upon Tyne, NE2 4HH, United Kingdom
No email / No phone
Status: Recruiting
Phoenix, Arizona, 85054, United States
No email / No phone
Status: Withdrawn
Santa Rosa, California, 95403, United States
No email / No phone
Status: Recruiting
Duarte, California, 91010, United States
No email / No phone
Status: Withdrawn
Aurora, Colorado, 80045, United States
No email / No phone
Status: Recruiting
Jacksonville, Florida, 32224, United States
No email / No phone
Status: Recruiting
Atlanta, Georgia, 30322, United States
No email / No phone
Status: Recruiting
Chicago, Illinois, 60637, United States
No email / No phone
Status: Recruiting
Baltimore, Maryland, 21231, United States
No email / No phone
Status: Not yet recruiting
Rochester, Minnesota, 55905, United States
No email / No phone
Status: Recruiting
St Louis, Missouri, 63110, United States
No email / No phone
Status: Recruiting
East Brunswick, New Jersey, 08816, United States
No email / No phone
Status: Withdrawn
Valhalla, New York, 10595, United States
No email / No phone
Status: Recruiting
Commack, New York, 11725, United States
No email / No phone
Status: Recruiting
Cleveland, Ohio, 44124, United States
No email / No phone
Status: Recruiting
Columbus, Ohio, 43210, United States
No email / No phone
Status: Not yet recruiting
Cleveland, Ohio, 44195, United States
No email / No phone
Status: Recruiting
Cleveland, Ohio, 44111, United States
No email / No phone
Status: Recruiting
Independence, Ohio, 44131, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97239, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97225, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97213, United States
No email / No phone
Status: Recruiting
Philadelphia, Pennsylvania, 19104, United States
No email / No phone
Status: Recruiting
Houston, Texas, 77030, United States
No email / No phone
Status: Recruiting
Fairfax, Virginia, 22031, United States
No email / No phone
Status: Recruiting