- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03762018
BEAT-meso: Bevacizumab and Atezolizumab in Malignant Pleural Mesothelioma (BEAT-meso)
A Multicentre Randomised Phase III Trial Comparing Atezolizumab Plus Bevacizumab and Standard Chemotherapy Versus Bevacizumab and Standard Chemotherapy as First-line Treatment for Advanced Malignant Pleural Mesothelioma
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Leuven, Belgium
- University Hospital Leuven
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Liege, Belgium
- CHU Liege
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Bordeaux, France
- Unicancer - Institut Bergonie
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Caen, France
- Caen- CHU
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Le Mans, France
- Le Mans - CHG
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Lyon, France
- Lyon - Centre Léon Bérard
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Marseille, France
- Hospital Nord
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Paris, France
- Curie Cancer Center Paris
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Toulouse, France
- Toulouse - CHU
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Tours, France
- Tours - CHU
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Alessandria, Italy
- SS Antonio e Biagio e Cesare Arrigo Hospital
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Bari, Italy
- IRCCS Instituto Tumori Giovanni Paolo II
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Milan, Italy
- Fondazione IRCCS Istituto Nazionale die Tumori
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Milan, Italy
- Instituto Europeo di Oncologia (IEO)
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Treviso, Italy
- AULSS2 Marca Trevigiana Treviso
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Turin, Italy
- University Hospital of Turin
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Alicante, Spain
- Alicante University Hospital ISABIAL
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Barcelona, Spain
- ICO Hospitalet
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Barcelona, Spain
- Vall Hebron University Hospital/Vall Hebron Institue Oncology
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Majadahonda, Spain
- Puerta de Hierro Hospital
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Sabadell, Spain
- Hospital Parc Tauli Sabadell
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Seville, Spain
- Virgen del Rocio
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Vigo, Spain
- Complexo Hospitalario Universitario de Vigo
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Aarau, Switzerland
- Kantonsspital Aarau
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Bellinzona, Switzerland
- Istituto Oncologica della Svizzera Italiana
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Bern, Switzerland
- Ferdinando Cerciello
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Chur, Switzerland
- Kantonsspital Graubünden
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Lausanne, Switzerland
- CHUV
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Lucerne, Switzerland
- Luzerner Kantonsspital
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Saint Gallen, Switzerland
- Kantonsspital St. Gallen
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Winterthur, Switzerland
- Kantonsspital Winterthur
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Zürich, Switzerland
- UniversitätSpital Zürich
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Cambridge, United Kingdom
- Addenbrooke's Hospital
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Liverpool, United Kingdom
- Clatterbridge Cancer Centre
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London, United Kingdom
- Guy's and St Thomas' Hospital
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London, United Kingdom
- Royal Marsden Hospital (Fulham Road)
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London, United Kingdom
- Royal Marsden Hospital (Sutton)
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Maidstone, United Kingdom
- Kent Oncology Centre
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Manchester, United Kingdom
- Wythenshawe Hospital
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Plymouth, United Kingdom
- Plymouth Hospitals Nhs Trust
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Sheffield, United Kingdom
- Weston Park Hospital
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Truro, United Kingdom
- Royal Cornwall Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 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
|
Carboplatin belongs to the group of medicines known as alkylating agents.
Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.
Other Names:
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.
Other Names:
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.
Other Names:
|
Experimental: 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
|
Carboplatin belongs to the group of medicines known as alkylating agents.
Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.
Other Names:
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.
Other Names:
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.
Other Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: From date of randomisation until death from any cause, assessed up to 58 months
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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).
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From date of randomisation until death from any cause, assessed up to 58 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS) according to the mRECIST v1.1
Time Frame: From date of randomisation until documented progression or death, if progression is not documented, assessed up to 58 months
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PFS is defined as the time from the date of randomisation until documented progression (according to the mRECIST v1.1) or death, if progression is not documented.
Censoring (for participants without a PFS/death event) will occur at the date of last tumour assessment.
Patients without a post-baseline tumour assessment will be censored at the date of randomization (plus 1 day).
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From date of randomisation until documented progression or death, if progression is not documented, assessed up to 58 months
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Objective Response Rate (ORR)
Time Frame: 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
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Defined as the percentage of patients that achieve a best overall response [complete response (CR) or partial response (PR)] evaluated according to the mRECIST v1.1 across all post-randomization time-points until the end of protocol treatment or, as an alternative approach, until the end of follow-up.
Confirmation of response will not be required.
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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
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Disease Control (DC) at 24 weeks
Time Frame: 24 weeks after protocol treatment start
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Defined as complete or partial response, or disease stabilisation at 24 weeks.
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24 weeks after protocol treatment start
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Time to Treatment Failure (TTF)
Time Frame: From randomisation until discontinuation of protocol treatment for any reason, assessed up to 58 months
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Defined as the time from the date of randomisation to discontinuation of protocol treatment for any reason (including progression of disease, death, discontinuation of at least one of the drugs consisting the treatment combination due to any reason, such as toxicity or refusal).
Censoring will occur at the last follow-up date.
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From randomisation until discontinuation of protocol treatment for any reason, assessed up to 58 months
|
Duration of Response (DoR)
Time Frame: From date of first documentation of objective response until date of first documented progression/ relapse or death, assessed up to 58 months
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Defined as the interval from the date of first documentation of objective response (complete response or partial response, according to the mRECIST v1.1) to the date of first documented progression/ relapse or death.
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From date of first documentation of objective response until date of first documented progression/ relapse or death, assessed up to 58 months
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Number of participants with treatment related adverse events according to Common Toxicity Criteria for Adverse Events (CTCAE) v5.0
Time Frame: Assessed from the date of informed consent until 90 days after protocol treatment discontinuation. Analysed at 58 months after randomisation of the first patient
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Assessed through analysis of the worst grade of toxicity/adverse events and will include all participants who received at least one dose of protocol treatment.
Adverse events leading to dose interruption, withdrawal of protocol treatment and deaths, laboratory parameters and abnormalities and vital signs over the whole treatment period will be assessed and graded according to CTCAE v5.0 criteria.
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Assessed from the date of informed consent until 90 days after protocol treatment discontinuation. Analysed at 58 months after randomisation of the first patient
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Enriqueta Felip, MD-PhD, Vall d'Hebron University Hospital
- Study Chair: Sanjay Popat, PhD, MBBS, Royal Marsden NHS Foundation Trust
Publications and helpful links
General Publications
- 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.
- 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.
- 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. Erratum In: Lancet. 2016 Apr 2;387(10026):e24.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: J Thorac Oncol. 2019 Mar;14(3):560.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Adenoma
- Neoplasms, Mesothelial
- Pleural Neoplasms
- Mesothelioma
- Mesothelioma, Malignant
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Immune Checkpoint Inhibitors
- Folic Acid Antagonists
- Carboplatin
- Bevacizumab
- Pemetrexed
- Atezolizumab
Other Study ID Numbers
- ETOP 13-18
- 2018-002180-25 (EudraCT Number)
- MO40388 (Other Identifier: F.Hoffman-La Roche Ltd)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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