Clinical trial NCT06097728: MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Unresectable Pleural Mesothelioma
Keywords: Mesothelioma
Pleural Mesothelioma
Unresectable Pleural Mesothelioma
Advanced pleural mesothelioma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-10-24
Enrollment: 825
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS) in experimental arm relative to comparator arm
timeFrame: up to approximately 61 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to approximately 61 months
measure: Progression Free Survival (PFS)
timeFrame: up to approximately 61 months
measure: Landmark OS
timeFrame: 12, 18, 24, 36 months
measure: Landmark PFS
timeFrame: 6, 12, 18, 24 months
measure: Overall Response Rate (ORR)
timeFrame: up to approximately 61 months
measure: Duration of Response (DoR)
timeFrame: up to approximately 61 months
measure: PFS2
timeFrame: up to approximately 61 months
measure: Patient-reported physical functioning
timeFrame: up to approximately 61 months.
measure: Disease-related symptoms using EORTC IL305 (Q1)
timeFrame: Up to approximately 61 months.
measure: Disease-related symptoms using PRO-CTCAE (Q1, 5, 6, 9)
timeFrame: Up to approximately 61 months
measure: Patient-reported role functioning using EORTC QLQ-C30 RF subscale (IL305 Q2 3)
timeFrame: up to approximately 61 months
measure: Patient-reported HRQoL (Health-related Quality of Life) using EORTC QLQ-C30 HRQoL subscale (IL305 Q7-8)
timeFrame: Up to approximately 61 months
measure: Immunogenicity of volrustomig
timeFrame: up to approximately 61 months
measure: Incidence of Adverse Events (AEs) AEs graded by CTCAE version 5.0
timeFrame: Up to approximately 61 months
measure: Area under the curve (AUC)
timeFrame: Up to approximately 61 months
measure: Maximum plasma concentration of the drug (Cmax)
timeFrame: Up to approximately 61 months
measure: The time taken to reach the maximum concentration (Tmax)
timeFrame: Up to approximately 61 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Duarte
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: East Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Commack
country: United States
facility: Research Site
state: New York
city: Valhalla
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Independence
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Chermside
country: Australia
facility: Research Site
city: Clayton
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Westmead
country: Australia
facility: Research Site
city: Anderlecht
country: Belgium
facility: Research Site
city: Antwerpen
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Hasselt
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Sint-Niklaas
country: Belgium
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Joao Pessoa
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Santo Andre
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Aarhus N
country: Denmark
facility: Research Site
city: Copenhagen
country: Denmark
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Creteil Cedex
country: France
facility: Research Site
city: Le Mans Cedex
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille Cedex 20
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Saint Herblain
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Georgsmarienhuette
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Muenster
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Alessandria
country: Italy
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Varese
country: Italy
facility: Research Site
city: Amagasaki-shi
country: Japan
facility: Research Site
city: Hakodate-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kitaadachi-gun
country: Japan
facility: Research Site
city: Kitakyushu-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nishinomiya-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Tokyo
country: Japan
facility: Research Site
city: Ube-shi
country: Japan
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Eindhoven
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Lørenskog
country: Norway
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Bystra
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Amanzimtoti
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Kimberly
country: South Africa
facility: Research Site
city: Polokwane
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Barakaldo
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Baden
country: Switzerland
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Fribourg
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Diyarbakir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cardiff, Wales
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Middlesborough
country: United Kingdom
facility: Research Site
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Research Site
city: Portsmouth
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Memorial Slone Kettering (MSK) Cancer Centre
name: Marjorie G Zauderer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lille University
name: Arnaud Scherpereel, MD
role: PRINCIPAL_INVESTIGATOR
References: