Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)
A Randomized, Open-label, Active-controlled, Phase II Study of Intravenous Anetumab Ravtansine (BAY 94-9343) or Vinorelbine in Patients With Advanced or Metastatic Malignant Pleural Mesothelioma Overexpressing Mesothelin and Progressed on First Line Platinum/Pemetrexed-based Chemotherapy
2 other identifiers
interventional
248
14 countries
75
Brief Summary
The main purpose of the 15743 study is to assess efficacy and safety of anetumab ravtansine versus vinorelbine in progression free survival in patients with stage IV mesothelin overexpressing malignant pleural mesothelioma (MPM). 210 eligible patients will be randomized to receive either anetumab ravtansine every three weeks or weekly vinorelbine. Treatment will continue until centrally confirmed disease progression or until another criterion is met for withdrawal from the study. Patients will enter follow up phase to capture safety and endpoint data as required. Efficacy will be measured by evaluating progression free survival from randomization. Radiological tumor assessments will be performed at defined time points until the patient's disease progresses. Blood samples will be collected for safety, pharmacokinetic and biomarker analysis. Archival or fresh biopsy tissue may also be collected for central pathology review and biomarkers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2015
Typical duration for phase_2
75 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2015
CompletedFirst Posted
Study publicly available on registry
November 20, 2015
CompletedStudy Start
First participant enrolled
December 3, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 6, 2019
CompletedResults Posted
Study results publicly available
July 17, 2020
CompletedNovember 4, 2020
October 1, 2020
1.5 years
November 9, 2015
May 22, 2020
October 28, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS), [95% CI]
Progression-free survival (PFS), defined as time from randomization until disease progression according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) for Malignant pleural mesothelioma (MPM) per blinded central radiology review, or death. Only descriptive analysis of OS was repeated in the follow-up period.
From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)
Secondary Outcomes (12)
Overall Survival (OS), [95% CI]
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause; one-sided log-rank test stratified by time to progression (TTP) on first line treatment.
Objective Response Rate (ORR)
up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause.
Disease Control Rate (DCR)
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Duration of Response (DOR)
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Durable Response Rate (DRR)
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
- +7 more secondary outcomes
Study Arms (2)
BAY94-9343
EXPERIMENTALDrug Anetumab ravtansine given Intravenously (IV)
Vinorelbine
ACTIVE COMPARATORDrug Vinorelbine given Intravenously
Interventions
Starting dose: 6.5 mg/kg administered as IV infusion over 1 h every 3 weeks until disease progression or treatment withdrawal for any reason. Dose reductions are permitted.
Starting dose: 30mg/m\^2 administered as an IV infusion over 6 to 10 min every week until disease progression or treatment withdrawal for any reason. Dose reductions are permitted per standard practise.
Eligibility Criteria
You may qualify if:
- Histological documentation of malignant pleural mesothelioma (MPM) overexpressing mesothelin
- Unresectable locally advanced or metastatic MPM after locally confirmed progression on 1st line treatment with platinum in combination with pemetrexed.
- Patients must have measurable disease
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Life expectancy of at least 3 months.
- Adequate bone marrow, liver and renal function
- Left ventricular ejection fraction (LVEF) ≥ 50% or the lower limit of normal (LLN) according to local institution ranges of normality.
You may not qualify if:
- More than 1 previous systemic anti-cancer therapy line
- Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the investigator in consultation with the ophthalmologist.
- Brain metastases, meningeal tumours or other metastases in the central nervous system
- Evidence of history of bleeding diathesis.
- Ongoing or active infection (bacterial, fungal, or viral) of National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade \> 2.
- Pre-existing cardiac conditions
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
- ImmunoGen and MorphoSyscollaborator
Study Sites (75)
Unknown Facility
La Jolla, California, 92093-1503, United States
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Aurora, Colorado, 80045, United States
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Norwich, Connecticut, 06360, United States
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Tampa, Florida, 33612, United States
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Chicago, Illinois, 60612, United States
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Chicago, Illinois, 60637, United States
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New Orleans, Louisiana, 70121, United States
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Bethesda, Maryland, 20814, United States
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Rochester, Minnesota, 55905, United States
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Buffalo, New York, 14263-0001, United States
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New York, New York, 10016, United States
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Durham, North Carolina, 27710, United States
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Cleveland, Ohio, 44195, United States
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Dallas, Texas, 75251, United States
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Houston, Texas, 77030, United States
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St Leonards, New South Wales, 2065, Australia
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Woolloogabba, Queensland, 4102, Australia
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Adelaide, South Australia, 5043, Australia
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Richmond, Victoria, 3122, Australia
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Nedlands, Western Australia, 6009, Australia
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Bruxelles - Brussel, 1200, Belgium
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Edegem, 2650, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Sint-Niklaas, 9100, Belgium
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Calgary, Alberta, T2N 4N2, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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London, Ontario, N6A 4L6, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Helsinki, 00290, Finland
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Turku, 20520, Finland
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Vaasa, 65130, Finland
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Bordeaux, 33076, France
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Caen, 14076, France
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Lille, 59037, France
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Marseille, 13915, France
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Paris, 75018, France
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Paris, 75020, France
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Pierre-Bénite, 69495, France
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Pordenone, Friuli Venezia Giulia, 33081, Italy
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Bergamo, Lombardy, 24125, Italy
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Milan, Lombardy, 20089, Italy
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Milan, Lombardy, 20133, Italy
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Monza Brianza, Lombardy, 20900, Italy
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Turin, Piedmont, 10043, Italy
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Siena, Tuscany, 53100, Italy
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Amsterdam, 1066 CX, Netherlands
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Rotterdam, 3015 CE, Netherlands
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Gdansk, 80-952, Poland
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Krakow, 31-202, Poland
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Krakow, 31-501, Poland
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Szczecin, 70-891, Poland
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Omsk, 644013, Russia
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Yekaterinburg, 620036, Russia
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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A Coruña, 15006, Spain
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Alicante, 03010, Spain
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Barcelona, 08035, Spain
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Madrid, 28041, Spain
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Málaga, 29010, Spain
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Adana, 01330, Turkey (Türkiye)
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Ankara, 06100, Turkey (Türkiye)
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Eskişehir, 26480, Turkey (Türkiye)
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Istanbul, 34899, Turkey (Türkiye)
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Malatya, 44280, Turkey (Türkiye)
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Yenimahalle, 06200, Turkey (Türkiye)
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Plymouth, Devon, PL6 8DH, United Kingdom
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Maidstone, Kent, ME16 9QQ, United Kingdom
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Leicester, Leicestershire, LE1 5WW, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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London, SE1 9RT, United Kingdom
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Manchester, M23 9LT, United Kingdom
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Newcastle upon Tyne, NE7 7DN, United Kingdom
Related Publications (1)
Kindler HL, Novello S, Bearz A, Ceresoli GL, Aerts JGJV, Spicer J, Taylor P, Nackaerts K, Greystoke A, Jennens R, Calabro L, Burgers JA, Santoro A, Cedres S, Serwatowski P, Ponce S, Van Meerbeeck JP, Nowak AK, Blumenschein G Jr, Siegel JM, Kasten L, Kochert K, Walter AO, Childs BH, Elbi C, Hassan R, Fennell DA. Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. Lancet Oncol. 2022 Apr;23(4):540-552. doi: 10.1016/S1470-2045(22)00061-4.
PMID: 35358455DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- Bayer AG
Study Officials
- STUDY DIRECTOR
Bayer Study Director
Bayer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2015
First Posted
November 20, 2015
Study Start
December 3, 2015
Primary Completion
May 31, 2017
Study Completion
September 6, 2019
Last Updated
November 4, 2020
Results First Posted
July 17, 2020
Record last verified: 2020-10