BEAT-meso: Bevacizumab and Atezolizumab in Malignant Pleural Mesothelioma

NCT03762018 | Completed Phase 3 DMC

• 3 other identifiers: ETOP 13-182018-002180-25MO40388
• Study Type: interventional
• Target: 401
• Locations: 6 countries
• Sites: 42

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.

Conditions

Pleural Mesothelioma Malignant Advanced

Keywords

MPM

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival is defined as the time from the date of randomisation until death from any cause. Data for patients who are not reported as having died at the date of analysis will be censored at the date when they were last known to be alive. Data for patients without post-baseline information will be censored at the date of randomization (plus 1 day).

  From date of randomisation until death from any cause, assessed up to 58 months

Secondary Outcomes (6)

• Progression-free Survival (PFS) according to the mRECIST v1.1

  From date of randomisation until documented progression or death, if progression is not documented, assessed up to 58 months

• Objective Response Rate (ORR)

  From start of protocol treatment acorss all time-points until end of protocol treatment or, as an alternative approach, until the end of follow-up, assessed up to 58 months

• Disease Control (DC) at 24 weeks

  24 weeks after protocol treatment start

• Time to Treatment Failure (TTF)

  From randomisation until discontinuation of protocol treatment for any reason, assessed up to 58 months

• Duration of Response (DoR)

  From date of first documentation of objective response until date of first documented progression/ relapse or death, assessed up to 58 months

Study Arms (2)

Bevacizumab plus chemotherapy

ACTIVE COMPARATOR

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

Drug: Carboplatin; Drug: Pemetrexed; Drug: Bevacizumab

Atezolizumab plus bevacizumab plus chemotherapy

EXPERIMENTAL

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

Drug: Carboplatin; Drug: Pemetrexed; Drug: Bevacizumab; Drug: Atezolizumab

Interventions

Carboplatin DRUG

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

Also known as: Carboplatin Accord

Atezolizumab plus bevacizumab plus chemotherapy; Bevacizumab plus chemotherapy

Pemetrexed 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.

Also known as: Alimta

Atezolizumab plus bevacizumab plus chemotherapy; Bevacizumab plus chemotherapy

Bevacizumab 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.

Also known as: Avastin

Atezolizumab plus bevacizumab plus chemotherapy; Bevacizumab plus chemotherapy

Atezolizumab 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.

Also known as: Tecentriq, RO5541267

Atezolizumab plus bevacizumab plus chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Hoffmann-La Roche: collaborator

Study Sites (42)

University Hospital Leuven

Leuven, Belgium

Location

CHU Liege

Liège, Belgium

Location

Unicancer - Institut Bergonie

Bordeaux, France

Location

Caen- CHU

Caen, France

Location

Le Mans - CHG

Le Mans, France

Location

Lyon - Centre Léon Bérard

Lyon, France

Location

Hospital Nord

Marseille, France

Location

Curie Cancer Center Paris

Paris, France

Location

Toulouse - CHU

Toulouse, France

Location

Tours - CHU

Tours, France

Location

SS Antonio e Biagio e Cesare Arrigo Hospital

Alessandria, Italy

Location

IRCCS Instituto Tumori Giovanni Paolo II

Bari, Italy

Location

Fondazione IRCCS Istituto Nazionale die Tumori

Milan, Italy

Location

Instituto Europeo di Oncologia (IEO)

Milan, Italy

Location

AULSS2 Marca Trevigiana Treviso

Treviso, Italy

Location

University Hospital of Turin

Turin, Italy

Location

Alicante University Hospital ISABIAL

Alicante, Spain

Location

ICO Hospitalet

Barcelona, Spain

Location

Vall Hebron University Hospital/Vall Hebron Institue Oncology

Barcelona, Spain

Location

Puerta de Hierro Hospital

Majadahonda, Spain

Location

Hospital Parc Tauli Sabadell

Sabadell, Spain

Location

Virgen del Rocio

Seville, Spain

Location

Complexo Hospitalario Universitario de Vigo

Vigo, Spain

Location

Kantonsspital Aarau

Aarau, Switzerland

Location

Istituto Oncologica della Svizzera Italiana

Bellinzona, Switzerland

Location

Ferdinando Cerciello

Bern, Switzerland

Location

Kantonsspital Graubünden

Chur, Switzerland

Location

CHUV

Lausanne, Switzerland

Location

Luzerner Kantonsspital

Lucerne, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

Location

Kantonsspital Winterthur

Winterthur, Switzerland

Location

UniversitätSpital Zürich

Zurich, Switzerland

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

Guy's and St Thomas' Hospital

London, United Kingdom

Location

Royal Marsden Hospital (Fulham Road)

London, United Kingdom

Location

Royal Marsden Hospital (Sutton)

London, United Kingdom

Location

Kent Oncology Centre

Maidstone, United Kingdom

Location

Wythenshawe Hospital

Manchester, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Related Publications (11)

• 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.

  PMID: 12860938 BACKGROUND

• 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.

  PMID: 26719230 BACKGROUND

• 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.

  PMID: 23860535 BACKGROUND

• 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.

  PMID: 26205340 BACKGROUND

• 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.

  PMID: 26826488 BACKGROUND

• 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.

  PMID: 27571927 BACKGROUND

• 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.

  PMID: 17534390 BACKGROUND

• 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.

  PMID: 18227828 BACKGROUND

• 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.

  PMID: 23977545 BACKGROUND

• 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.

  PMID: 29753121 BACKGROUND

• 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.

  PMID: 33358660 DERIVED

MeSH Terms

Interventions

Carboplatin; Pemetrexed; Bevacizumab; atezolizumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Enriqueta Felip, MD-PhD

  Vall d'Hebron University Hospital

  STUDY CHAIR

• Sanjay Popat, PhD, MBBS

  Royal Marsden NHS Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: December 3, 2018
• Study Start: April 30, 2019
• Primary Completion: September 1, 2023
• Study Completion: November 18, 2024
• Last Updated: June 4, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6); ES (7); CH (9); FR (8); BE (2); GB (10)