BEAT-meso: Bevacizumab and Atezolizumab in Malignant Pleural Mesothelioma

NCT ID: NCT03762018

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 401 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-30
• Study Completion Date: 2024-11-18

Brief Summary

The aim of this clinical trial is to assess the effect of treatment with a monoclonal antibody called atezolizumab in patients diagnosed with a type of lung cancer called malignant pleural mesothelioma. The efficacy (whether the treatment works), safety and tolerability (side effects of treatment) of atezolizumab plus bevacizumab in combination with standard chemotherapy versus bevacizumab in combination with standard chemotherapy will be investigated.

Detailed Description

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer arising from the mesothelial surface of the pleura. In Europe, the incidence is about 20 per million and is almost always caused by asbestos exposure, with a usual lag time of 30 years between exposure and presentation. Patients diagnosed with advanced MPM have limited treatment options, representing a strict unmet need. Despite decades of clinical research, cytotoxic chemotherapy remains one of the few therapeutic options that has been proven to improve survival in advanced MPM in a randomised controlled trial.

The combination of cisplatin and pemetrexed has become standard first-line therapy worldwide for patients who are not suitable for aggressive surgery or in whom chemotherapy is recommended as part of a multimodality regimen. Carboplatin is often substituted for cisplatin, due to simpler and shorter administration and assumption of a more favourable toxicity profile based on experience in other diseases. Patients with MPM have limited treatment options, representing a strict unmet need.

An antibody is a common type of protein usually made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. The two monoclonal antibodies (atezolizumab and bevacizumab) used in this trial are laboratory-produced antibodies. Atezolizumab is engineered to attach to immune cells to stimulate their activity against cancer cells.

Atezolizumab and bevacizumab are both approved by the European Medicines Agency for the treatment of lung and other cancers. The addition of atezolizumab to bevacizumab plus standard chemotherapy for the treatment of MPM is being investigated in this trial.

All participants will receive 4-6 cycles of standard chemotherapy consisting of carboplatin AUC 5 (area under the plasma concentration versus time curve) plus pemetrexed 500mg/m^2 given intravenously, on day 1 of every 3 week cycle for about 12 to 18 weeks.

Participants will be randomly assigned to one of two treatment groups:

Treatment 1

• Bevacizumab 15 mg/kg intravenously on day 1 of every 3-week cycle, plus
• 4-6 cycles of chemotherapy

OR

Treatment 2

• Atezolizumab 1200 mg fixed dose intravenously on day 1 of every 3-week cycle, plus
• Bevacizumab 15 mg/kg, intravenously on day 1 of every 3-week cycle, plus
• 4-6 cycles of chemotherapy

Participants will continue to receive treatment until disease progression, or until treatment is stopped at the request of the participant or treating doctor, or the participant withdraws consent.

A total of 400 participants from approximately 45 centres in Europe are expected to be included in this trial which will take approximately 6 years to be completed after the first participant is enrolled.

Conditions

Pleural Mesothelioma Malignant Advanced

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bevacizumab plus chemotherapy

Bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m\^2 intravenously on day 1 every 3 weeks

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin belongs to the group of medicines known as alkylating agents. Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.

Pemetrexed

Intervention Type: DRUG

Pemetrexed is a type of drug known as an anti metabolite. It stops cells making and repairing DNA so they can't grow and multiply.

Bevacizumab

Intervention Type: DRUG

Bevacizumab is an angiogenesis inhibitor. It works by targeting a protein called vascular endothelial growth factor (VEGF) that helps cancers form new blood vessels. By stopping this process, bevacizumab 'suffocates' the blood supply to the cancer, shrinking it and stopping it from growing.

Atezolizumab plus bevacizumab plus chemotherapy

Atezolizumab 1200mg intravenously on day 1 every 3 weeks plus bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m\^2 intravenously on day 1 every 3 weeks

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Carboplatin belongs to the group of medicines known as alkylating agents. Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.

Pemetrexed

Intervention Type: DRUG

Pemetrexed is a type of drug known as an anti metabolite. It stops cells making and repairing DNA so they can't grow and multiply.

Bevacizumab

Intervention Type: DRUG

Bevacizumab is an angiogenesis inhibitor. It works by targeting a protein called vascular endothelial growth factor (VEGF) that helps cancers form new blood vessels. By stopping this process, bevacizumab 'suffocates' the blood supply to the cancer, shrinking it and stopping it from growing.

Atezolizumab

Intervention Type: DRUG

Atezolizumab is in a class of medications called monoclonal antibodies. It works by blocking the action of a certain protein in cancer cells. This helps the immune system to fight against the cancer cells, and helps to slow tumor growth.

Interventions

Carboplatin

Carboplatin belongs to the group of medicines known as alkylating agents. Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.

Intervention Type: DRUG

Pemetrexed

Pemetrexed is a type of drug known as an anti metabolite. It stops cells making and repairing DNA so they can't grow and multiply.

Intervention Type: DRUG

Bevacizumab

Bevacizumab is an angiogenesis inhibitor. It works by targeting a protein called vascular endothelial growth factor (VEGF) that helps cancers form new blood vessels. By stopping this process, bevacizumab 'suffocates' the blood supply to the cancer, shrinking it and stopping it from growing.

Intervention Type: DRUG

Atezolizumab

Atezolizumab is in a class of medications called monoclonal antibodies. It works by blocking the action of a certain protein in cancer cells. This helps the immune system to fight against the cancer cells, and helps to slow tumor growth.

Intervention Type: DRUG

Other Intervention Names

Carboplatin Accord; Alimta; Avastin; Tecentriq; RO5541267

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed advanced malignant pleural mesothelioma (all histological subtypes are eligible)
• Not amenable for radical surgery based on local standards
• Evaluable disease or measurable disease as assessed according to the modified response evaluation criteria for solid tumours for mesothelioma (mRECIST) v1.1
• Availability of tumour tissue for translational research
• Age >18 years
• Performance Status 0-1
• Life expectancy >3 months
• Adequate haematological, renal and liver function
• Completed baseline quality of life (QoL) questionnaire
• Women of childbearing potential and sexually active men must agree to use highly effective contraception
• Able to understand and give written informed consent and comply with trial procedures

Exclusion Criteria

• Prior treatment for malignant pleural mesothelioma. Prior radiotherapy for symptom control is allowed, but the irradiated lesion cannot be used as target lesion. If the patient has another target lesion, the patient is eligible.
• Treatment with systemic immune-stimulatory agents within 4 weeks or five half-lives of the drug prior to randomisation and during protocol treatment.
• Treatment with systemic immunosuppressive medications within 2 weeks prior to randomisation and during protocol treatment.
• Previous allogeneic tissue/solid organ transplant
• Live vaccines within 4 weeks prior to first dose of protocol treatment
• Inadequately controlled hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease within 6 months prior to randomisation
• History of haemoptysis
• Evidence of bleeding diathesis or coagulopathy
• Active autoimmune disease that has required systemic treatment in past 2 years
• History of active diverticulitis
• Previous treatment with atezolizumab and/or bevacizumab or parallel participation in other interventional clinical trial with atezolizumab and/or bevacizumab.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enriqueta Felip, MD-PhD

Role: STUDY_CHAIR

Vall d'Hebron University Hospital

Sanjay Popat, PhD, MBBS

Role: STUDY_CHAIR

Royal Marsden NHS Foundation Trust

Locations

University Hospital Leuven

Leuven, , Belgium

CHU Liege

Liège, , Belgium

Unicancer - Institut Bergonie

Bordeaux, , France

Caen- CHU

Caen, , France

Le Mans - CHG

Le Mans, , France

Lyon - Centre Léon Bérard

Lyon, , France

Hospital Nord

Marseille, , France

Curie Cancer Center Paris

Paris, , France

Toulouse - CHU

Toulouse, , France

Tours - CHU

Tours, , France

SS Antonio e Biagio e Cesare Arrigo Hospital

Alessandria, , Italy

IRCCS Instituto Tumori Giovanni Paolo II

Bari, , Italy

Fondazione IRCCS Istituto Nazionale die Tumori

Milan, , Italy

Instituto Europeo di Oncologia (IEO)

Milan, , Italy

AULSS2 Marca Trevigiana Treviso

Treviso, , Italy

University Hospital of Turin

Turin, , Italy

Alicante University Hospital ISABIAL

Alicante, , Spain

ICO Hospitalet

Barcelona, , Spain

Vall Hebron University Hospital/Vall Hebron Institue Oncology

Barcelona, , Spain

Puerta de Hierro Hospital

Majadahonda, , Spain

Hospital Parc Tauli Sabadell

Sabadell, , Spain

Virgen del Rocio

Seville, , Spain

Complexo Hospitalario Universitario de Vigo

Vigo, , Spain

Kantonsspital Aarau

Aarau, , Switzerland

Istituto Oncologica della Svizzera Italiana

Bellinzona, , Switzerland

Ferdinando Cerciello

Bern, , Switzerland

Kantonsspital Graubünden

Chur, , Switzerland

CHUV

Lausanne, , Switzerland

Luzerner Kantonsspital

Lucerne, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

UniversitätSpital Zürich

Zurich, , Switzerland

Addenbrooke's Hospital

Cambridge, , United Kingdom

Clatterbridge Cancer Centre

Liverpool, , United Kingdom

Guy's and St Thomas' Hospital

London, , United Kingdom

Royal Marsden Hospital (Fulham Road)

London, , United Kingdom

Royal Marsden Hospital (Sutton)

London, , United Kingdom

Kent Oncology Centre

Maidstone, , United Kingdom

Wythenshawe Hospital

Manchester, , United Kingdom

Plymouth Hospitals NHS Trust

Plymouth, , United Kingdom

Weston Park Hospital

Sheffield, , United Kingdom

Royal Cornwall Hospital

Truro, , United Kingdom

Countries

Belgium; France; Italy; Spain; Switzerland; United Kingdom

References

Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.

Reference Type: BACKGROUND

PMID: 12860938 (View on PubMed)

Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, Corre R, Monnet I, Gounant V, Riviere F, Janicot H, Gervais R, Locher C, Milleron B, Tran Q, Lebitasy MP, Morin F, Creveuil C, Parienti JJ, Scherpereel A; French Cooperative Thoracic Intergroup (IFCT). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-1414. doi: 10.1016/S0140-6736(15)01238-6. Epub 2015 Dec 21.

Reference Type: BACKGROUND

PMID: 26719230 (View on PubMed)

Ceresoli GL, Zucali PA, Mencoboni M, Botta M, Grossi F, Cortinovis D, Zilembo N, Ripa C, Tiseo M, Favaretto AG, Soto-Parra H, De Vincenzo F, Bruzzone A, Lorenzi E, Gianoncelli L, Ercoli B, Giordano L, Santoro A. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer. 2013 Aug 6;109(3):552-8. doi: 10.1038/bjc.2013.368. Epub 2013 Jul 16.

Reference Type: BACKGROUND

PMID: 23860535 (View on PubMed)

Melero I, Berman DM, Aznar MA, Korman AJ, Perez Gracia JL, Haanen J. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat Rev Cancer. 2015 Aug;15(8):457-72. doi: 10.1038/nrc3973.

Reference Type: BACKGROUND

PMID: 26205340 (View on PubMed)

Soto-Ortiz L, Finley SD. A cancer treatment based on synergy between anti-angiogenic and immune cell therapies. J Theor Biol. 2016 Apr 7;394:197-211. doi: 10.1016/j.jtbi.2016.01.026. Epub 2016 Jan 27.

Reference Type: BACKGROUND

PMID: 26826488 (View on PubMed)

Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, Hernandez G, Mier J, He X, Hodi FS, Denker M, Leveque V, Canamero M, Babitski G, Koeppen H, Ziai J, Sharma N, Gaire F, Chen DS, Waterkamp D, Hegde PS, McDermott DF. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun. 2016 Aug 30;7:12624. doi: 10.1038/ncomms12624.

Reference Type: BACKGROUND

PMID: 27571927 (View on PubMed)

Tsiouris A, Walesby RK. Malignant pleural mesothelioma: current concepts in treatment. Nat Clin Pract Oncol. 2007 Jun;4(6):344-52. doi: 10.1038/ncponc0839.

Reference Type: BACKGROUND

PMID: 17534390 (View on PubMed)

Fennell DA, Gaudino G, O'Byrne KJ, Mutti L, van Meerbeeck J. Advances in the systemic therapy of malignant pleural mesothelioma. Nat Clin Pract Oncol. 2008 Mar;5(3):136-47. doi: 10.1038/ncponc1039.

Reference Type: BACKGROUND

PMID: 18227828 (View on PubMed)

Nowak AK. Chemotherapy for malignant pleural mesothelioma: a review of current management and a look to the future. Ann Cardiothorac Surg. 2012 Nov;1(4):508-15. doi: 10.3978/j.issn.2225-319X.2012.10.05. No abstract available.

Reference Type: BACKGROUND

PMID: 23977545 (View on PubMed)

Armato SG 3rd, Nowak AK. Revised Modified Response Evaluation Criteria in Solid Tumors for Assessment of Response in Malignant Pleural Mesothelioma (Version 1.1). J Thorac Oncol. 2018 Jul;13(7):1012-1021. doi: 10.1016/j.jtho.2018.04.034. Epub 2018 May 9.

Reference Type: BACKGROUND

PMID: 29753121 (View on PubMed)

Uprety D. CheckMate 743: A Glimmer of Hope for Malignant Pleural Mesothelioma. Clin Lung Cancer. 2021 Mar;22(2):71-73. doi: 10.1016/j.cllc.2020.11.009. Epub 2020 Dec 2. No abstract available.

Reference Type: DERIVED

PMID: 33358660 (View on PubMed)

Other Identifiers

2018-002180-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO40388

Identifier Type: OTHER

Identifier Source: secondary_id

ETOP 13-18

Identifier Type: -

Identifier Source: org_study_id