Unresectable Pleural MesotheliomaPhase 3eVOLVE-MesoNCT06097728
MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma
A Phase 3 study testing Volrustomig, Pemetrexed and Carboplatin in people with Unresectable Pleural Mesothelioma, run by AstraZeneca at 151 sites in 21 countries.
Trial summary
This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of Volrustomig (MEDI5752) + Carboplatin + Pemetrexed vs the investigator's choice of platinum + Pemetrexed or Nivolumab + Ipilimumab in participants with unresectable pleural mesothelioma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable Pleural Mesothelioma
- What is being tested?
- Volrustomig, Pemetrexed and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 863 participants
- Where
- 151 sitesin 21 countries
- Study dates
- 9 Nov 2023to 16 Nov 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
151 sites in 21 countries.
151 sites in 21 countries
China22 sites
Research Site
Beijing, 100142
Research Site
Beijing, 100210
Research Site
Changsha, 410013
Research Site
Chengdu, 610042
Research Site
Guangzhou, 510100
Research Site
Hangzhou, 310022
Research Site
Harbin, 150049
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Kunming, 650118
Research Site
Lanzhou, 730000
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Ningbo, 315100
Research Site
Qingdao, 266003
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Shandong
Research Site
Shanghai, 200032
Research Site
Shenyang, 110044
Research Site
Taiyuan, 030000
Research Site
Taiyuan, 030032
Research Site
Tianjin, 300050
Research Site
Tianjin, 300060
Research Site
Wuhan, 430030
Research Site
Xi'an, 710061
Research Site
Zhengzhou, 450008
Research Site
Zhengzhou, 450052
United States14 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Aurora, Colorado, 80045
Research Site
Chicago, Illinois, 60637
Research Site
Columbus, Ohio, 43210
Research Site
Commack, New York, 11725
Research Site
Fairfax, Virginia, 22031
Research Site
Houston, Texas, 77030
Research Site
Jacksonville, Florida, 32224
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Portland, Oregon, 97213
Research Site
Portland, Oregon, 97225
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Rochester, Minnesota, 55905
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Santa Rosa, California, 95403
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St Louis, Missouri, 63110
Germany13 sites
Research Site
Berlin, 13125
Research Site
Berlin, 14109
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Bochum, 44791
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Cologne, 51109
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Essen, 45122
Research Site
Gauting, 82131
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Georgsmarienhütte, 49124
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Großhansdorf, 22927
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Hamburg, 21075
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Heidelberg, 69126
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Kiel, 24105
Research Site
Münster, 48153
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Regensburg, 93049
France12 sites
Research Site
Brest, 29200
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Créteil, 94010
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Le Mans, 72037
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Lille, 59037
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Lyon, 69373
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Marseille, 13015
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Montpellier, 34298
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Paris, 75877
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Rouen, 76031
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Saint-Herblain, 44800
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Strasbourg, 67091
Research Site
Toulouse, 31059
Japan12 sites
Research Site
Amagasaki-shi, 660-8550
Research Site
Hakodate-shi, 040-8611
Research Site
Hiroshima, 734-8551
Research Site
Kitaadachi-gun, 362-0806
Research Site
Kitakyushu-shi, 807-8555
Research Site
Matsuyama, 791-0280
Research Site
Nagoya, 466-8560
Research Site
Nishinomiya-shi, 663-8501
Research Site
Okayama, 702-8055
Research Site
Osakasayama-shi, 589-8511
Research Site
Tokyo, 104-0045
Research Site
Ube-shi, 755-0241
Italy10 sites
Research Site
Alessandria, 15100
Research Site
Bari, 70124
Research Site
Bergamo, 24125
Research Site
Milan, 20141
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Monza, 20052
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Orbassano, 10043
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Padova, 35128
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Parma, 43100
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Rozzano, 20089
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Varese, 21100
United Kingdom10 sites
Research Site
Cambridge, CB20QQ
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Leeds, LS9 7TF
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Leicester, LE1 5WW
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London, NW1 2PG
Research Site
London, SE1 9RT
Research Site
London, SW3 6JJ
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Manchester, M23 9LT
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Newcastle upon Tyne, NE2 4HH
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Portsmouth, PO6 3LY
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Taunton, TA1 5DA
South Africa7 sites
Research Site
Cape Town, 7570
Research Site
eManzimtoti, 4126
Research Site
Johannesburg, 2013
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Johannesburg, 2193
Research Site
Kimberly, 8301
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Pretoria, 0002
Research Site
Pretoria, 0081
Brazil6 sites
Research Site
Barretos, 14784-400
Research Site
Fortaleza, 60336-045
Research Site
Porto Alegre, 91350-200
Research Site
Rio de Janeiro, 22281-100
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Santo André, 09060-650
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São Paulo, 01246-000
Australia5 sites
Research Site
Chermside, 4032
Research Site
Clayton, 3168
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Melbourne, 3000
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Nedlands, 6009
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Westmead, 2145
Belgium5 sites
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Anderlecht, 1070
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Antwerp, 2020
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Ghent, 9000
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Hasselt, 3500
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Sint-Niklaas, 9100
Canada5 sites
Research Site
Edmonton, Alberta, T6G 1Z2
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Montreal, Quebec, H2X 0C1
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Ottawa, Ontario, K1H 8L6
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Québec, Quebec, G1V 4G5
Research Site
Toronto, Ontario, M5G 1X6
Switzerland5 sites
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Baden, CH-5405
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Basel, 4031
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Bern, 3010
Research Site
Fribourg, 1700
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Sankt Gallen, 9007
Poland4 sites
Research Site
Bystra, 43-360
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Olsztyn, 10-357
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Poznan, 60-569
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Warsaw, 02-781
Spain4 sites
Research Site
Barakaldo, 48903
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Barcelona, 8035
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Madrid, 28041
Research Site
Oviedo, 33011
Turkey (Türkiye)4 sites
Research Site
Ankara, 06280
Research Site
Ankara, 06800
Research Site
Diyarbakır, 21280
Research Site
Izmir, 35110
Netherlands3 sites
Research Site
Amsterdam, 1066CX
Research Site
Eindhoven, 5623EJ
Research Site
Rotterdam, 3015 GD
South Korea3 sites
Research Site
Seoul, 03080
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Taiwan3 sites
Research Site
Kaohsiung City, 80756
Research Site
Taichung, 40705
Research Site
Taipei, 10002
About this study
Official title: 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)
This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of Volrustomig (MEDI5752) + Carboplatin + Pemetrexed vs the investigator's choice of platinum + Pemetrexed or Nivolumab + Ipilimumab in participants with unresectable pleural mesothelioma.
Read the detailed description
Adult patients with histologically proven diagnosis of pleural mesothelioma with advanced unresectable disease are eligible to be enrolled. Patients will be randomized 1:1 to receive Volrustomig (MEDI5752) + Carboplatin + Pemetrexed or the investigator's choice of platinum+Pemetrexed or Nivolumab+Ipilimumab, based on their histology.
- Conditions
- Unresectable Pleural Mesothelioma
- Being tested
- Volrustomig, Pemetrexed, Carboplatin, Cisplatin, Nivolumab
- Keywords
- Mesothelioma, Pleural Mesothelioma, Unresectable Pleural Mesothelioma, Advanced pleural mesothelioma
- Medical subject headings
- Mesothelioma, Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VolrustomigDrug
Also called MEDI5752
MEDI5752: Administered as IV infusion
PemetrexedDrug
Also called Alimta
Alimta: Administered as IV infusion
CarboplatinDrug
Also called Paraplatin
Paraplatin: Administered as IV infusion
CisplatinDrug
Also called Platinol
Platinol: Administered as IV infusion
NivolumabDrug
Also called Opdivo
Opdivo: Administered as IV infusion
IpilimumabDrug
Also called Yervoy
Yervoy: Administered as IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Volrustomig + Carboplatin + pemetrexed | Experimental | Volrustomig in combination with carboplatin plus pemetrexed Receives: Drug: Volrustomig; Drug: Pemetrexed; Drug: Carboplatin |
| Investigator's choice of standard care | Active comparator | The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology. Receives: Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin; Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) in experimental arm relative to comparator arm
OS is defined as the time from randomization until the date of death due to any cause.
Measured: up to approximately 61 months
Secondary outcomes (17)
Overall Survival (OS)
OS is defined as the time from randomization until the date of death due to any cause.
Measured: up to approximately 61 months
Progression Free Survival (PFS)
PFS is defined as the time from randomization until progression per mRECIST 1.1 and/or RECIST 1.1 as assessed by the investigator at local site, or death due to any cause.
Measured: up to approximately 61 months
Landmark OS
Landmarks of OS12, OS18, OS24, and OS36.
Measured: 12, 18, 24, 36 months
Landmark PFS
Landmarks of PFS6, PFS12, PFS18, and PFS24
Measured: 6, 12, 18, 24 months
Overall Response Rate (ORR)
Proportion of participants who have a confirmed Complete Response or confirmed Partial Response, as determined by the investigator at local site per mRECIST 1.1 and/or RECIST 1.1.
Measured: up to approximately 61 months
Duration of Response (DoR)
DoR defined as the time from the date of first documented response until date of documented progression per mRECIST 1.1 and/or RECIST 1.1 as assessed by the investigator at local site or death due to any cause.
Measured: up to approximately 61 months
PFS2
PFS2 defined as the time from randomization to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.
Measured: up to approximately 61 months
Patient-reported physical functioning
TTD in physical functioning as measured by PROMIS (Patient Reported Outcomes Measurement Information System) Physical Function Short Form 8c. There are 8 questions each from a scale of 1 (unable to do) to a scale of 5 (With a little difficulty). The higher the scores the better the patient-reported physical functioning is.
Measured: up to approximately 61 months.
Disease-related symptoms using EORTC IL305 (Q1)
Change from baseline in disease-related symptoms as measured by individual symptom items from the EORTC (European Organisation For Research And Treatment Of Cancer) IL305 (Item Library 305) (Q1). It is scored from a 1 (not at all) to a 4 (very much). The higher the score the higher the disease-related symptoms.
Measured: Up to approximately 61 months.
Disease-related symptoms using PRO-CTCAE (Q1, 5, 6, 9)
Change from baseline in disease-related symptoms as measured by individual symptom items from the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) (Q1, 5, 6, 9). PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present). The higher the score the higher the disease-related symptoms.
Measured: Up to approximately 61 months
Patient-reported role functioning using EORTC QLQ-C30 RF subscale (IL305 Q2 3)
Change from baseline in functioning will be assessed by the following measure:
Role functioning: EORTC (European Organisation For Research And Treatment Of Cancer) QLQ (Quality of Life Questionnaire) -C30 RF (Role Functioning) subscale (IL305 Q2 3) (Item Library 305). The questions are from a scale of 1 (not at all) to 4 (very much). The lower the score the higher the patient-reported role functioning is.
Measured: up to approximately 61 months
Patient-reported HRQoL (Health-related Quality of Life) using EORTC QLQ-C30 HRQoL subscale (IL305 Q7-8)
Change from baseline in functioning will be assessed by the following measure:
HRQoL: EORTC (European Organisation For Research And Treatment Of Cancer) QLQ (Quality of Life Questionnaire) -C30 HRQoL subscale (IL305 Q7-8) (Item Library 305). The questions are from a scale of 1 (very poor) to 7 (excellent). The higher the score the higher the HRQoL.
Measured: Up to approximately 61 months
Immunogenicity of volrustomig
Incidence of Anti-Drug Antibodies against volrustomig.
Measured: up to approximately 61 months
Incidence of Adverse Events (AEs) AEs graded by CTCAE version 5.0
Incidence of Adverse Events (AEs) AEs graded by CTCAE (Common Terminology Criteria for Adverse Events) version 5.0. Grade refers to the severity of the AE. The CTCAE displays grade 1 (mild) through 5 (death related to AE). Grade 2 (moderate), Grade 3 (Severe) and Grade 4 (Life-threatening consequences).
Measured: Up to approximately 61 months
Area under the curve (AUC)
The concentration of MEDI5752 in serum will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
Measured: Up to approximately 61 months
Maximum plasma concentration of the drug (Cmax)
The concentration of MEDI5752 in serum will be determined (Cmax will be derived).
Measured: Up to approximately 61 months
The time taken to reach the maximum concentration (Tmax)
The concentration of MEDI5752 in serum will be determined (Tmax will be derived).
Measured: Up to approximately 61 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2023
- Study start9 Nov 2023
- Primary completion16 Nov 2028 (estimated)
- Study completion16 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, open-label, Phase III trial in participants with untreated unresectable pleural mesothelioma. Approximately 825 participants across histology subtypes will be randomized in a 1:1 ratio to receive volrustomig in combination with carboplatin plus pemetrexed or the investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 863 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marjorie G Zauderer, MD, Principal investigator, Memorial Slone Kettering (MSK) Cancer CentreArnaud Scherpereel, MD, Principal investigator, Lille University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06097728
- Sponsor's protocol ID
- D7988C00001
- Other IDs
- 2023-503231-17-00, 2023-000067-32, 2023
- Acronym
- eVOLVE-Meso
- Status last verified
- Oct 2026
- First submitted
- 4 Oct 2023
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.