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Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)

Primary Purpose

Mesothelioma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Anetumab ravtansine (BAY94-9343)
Vinorelbine
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mesothelioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

BAY94-9343

Vinorelbine

Arm Description

Drug Anetumab ravtansine given Intravenously (IV)

Drug Vinorelbine given Intravenously

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Survival (OS), [95% CI]
Overall survival (OS) was defined as time from randomization until death from any cause.
Objective Response Rate (ORR)
A patient is a responder if the patient has a confirmed best tumor response on-study of CR (Complete response) or PR (Partial response), as determined by the central radiological reviewer per mRECIST criteria. ORR in each treatment arm was defined as the number of responders divided by the number of randomized patients. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.
Disease Control Rate (DCR)
A patient has disease control if the patient has a best tumor response on-study of CR, PR, or SD (Stable disease). DCR was defined as a percentage of patients achieving CR, PR, or SD per mRECIST criteria, as determined by the central radiological reviewer. DCR was calculated in each treatment arm as the number of patients with disease control (a best tumor response on-study of CR, PR, or SD) divided by the number of randomized patients.
Duration of Response (DOR)
DOR was defined in responders as the time from central documentation of tumor response date of first response in the confirmation sequence) to the earlier of disease progression as determined by the central radiological reviewer, or death without centrally documented progression. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.
Durable Response Rate (DRR)
A durable responder was a responder (i.e. confirmed best tumor response on study of CR or PR) with duration of response of 180 days or more.
Percentage of Participants With Confirmed Improvement of Symptoms Characteristic of Mesothelioma
Improvement rate of symptoms characteristic of mesothelioma was defined as the number of patients with confirmed improvement of symptoms characteristic of mesothelioma (based on the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma, MDASI-MPM), divided by the number of patients evaluable for improvement of symptoms characteristic of mesothelioma.
Time to Worsening of Symptoms Characteristic of Mesothelioma
Time to worsening of symptoms characteristic of mesothelioma (TTWS) was defined in patients evaluable for assessing worsening of symptoms, as the time from randomization until the first worsening of symptoms characteristic of mesothelioma. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of symptoms were censored at the date of their last MDASI-MPM assessment with a non-missing (Composite Symptom Score) CSS.
Time to Worsening of Pain
Time to worsening of pain (TTWP) was defined in patients evaluable for assessing worsening of pain, as time from randomization until the first worsening of pain. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of pain were censored at the date of their last MDASI-MPM assessment with a non-missing pain score.
Percentage of Participants With Confirmed Improvement of Pain
Improvement rate of pain was defined as the number of patients with confirmed improvement of pain (based on the "pain at its worst" item of MDASI-MPM), divided by the number of patients evaluable for improvement of pain.
Percentage of Participant With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as all AEs starting or worsening within the treatment period.
Number of Deaths
TEAE(s) associated with a fatal outcome (CTCAE Grade 5) at the time of the data cut-off 06-Apr-2018.
Overall Survival (OS) - Addendum
Overall survival (OS) was defined as time from randomization until death from any cause; Only descriptive analyses of OS were repeated in with the data as of the 02 JUL 2019.

Full Information

First Posted
November 9, 2015
Last Updated
October 28, 2020
Sponsor
Bayer
Collaborators
ImmunoGen and MorphoSys
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1. Study Identification

Unique Protocol Identification Number
NCT02610140
Brief Title
Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 3, 2015 (Actual)
Primary Completion Date
May 31, 2017 (Actual)
Study Completion Date
September 6, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
Collaborators
ImmunoGen and MorphoSys

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesothelioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
248 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BAY94-9343
Arm Type
Experimental
Arm Description
Drug Anetumab ravtansine given Intravenously (IV)
Arm Title
Vinorelbine
Arm Type
Active Comparator
Arm Description
Drug Vinorelbine given Intravenously
Intervention Type
Drug
Intervention Name(s)
Anetumab ravtansine (BAY94-9343)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS), [95% CI]
Description
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.
Time Frame
From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)
Secondary Outcome Measure Information:
Title
Overall Survival (OS), [95% CI]
Description
Overall survival (OS) was defined as time from randomization until death from any cause.
Time Frame
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.
Title
Objective Response Rate (ORR)
Description
A patient is a responder if the patient has a confirmed best tumor response on-study of CR (Complete response) or PR (Partial response), as determined by the central radiological reviewer per mRECIST criteria. ORR in each treatment arm was defined as the number of responders divided by the number of randomized patients. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.
Time Frame
up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause.
Title
Disease Control Rate (DCR)
Description
A patient has disease control if the patient has a best tumor response on-study of CR, PR, or SD (Stable disease). DCR was defined as a percentage of patients achieving CR, PR, or SD per mRECIST criteria, as determined by the central radiological reviewer. DCR was calculated in each treatment arm as the number of patients with disease control (a best tumor response on-study of CR, PR, or SD) divided by the number of randomized patients.
Time Frame
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Title
Duration of Response (DOR)
Description
DOR was defined in responders as the time from central documentation of tumor response date of first response in the confirmation sequence) to the earlier of disease progression as determined by the central radiological reviewer, or death without centrally documented progression. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.
Time Frame
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Title
Durable Response Rate (DRR)
Description
A durable responder was a responder (i.e. confirmed best tumor response on study of CR or PR) with duration of response of 180 days or more.
Time Frame
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Title
Percentage of Participants With Confirmed Improvement of Symptoms Characteristic of Mesothelioma
Description
Improvement rate of symptoms characteristic of mesothelioma was defined as the number of patients with confirmed improvement of symptoms characteristic of mesothelioma (based on the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma, MDASI-MPM), divided by the number of patients evaluable for improvement of symptoms characteristic of mesothelioma.
Time Frame
up to approx. 30 months (data cut-off: 31-May-2017)
Title
Time to Worsening of Symptoms Characteristic of Mesothelioma
Description
Time to worsening of symptoms characteristic of mesothelioma (TTWS) was defined in patients evaluable for assessing worsening of symptoms, as the time from randomization until the first worsening of symptoms characteristic of mesothelioma. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of symptoms were censored at the date of their last MDASI-MPM assessment with a non-missing (Composite Symptom Score) CSS.
Time Frame
up to approx. 30 months (data cut-off: 31-May-2017)
Title
Time to Worsening of Pain
Description
Time to worsening of pain (TTWP) was defined in patients evaluable for assessing worsening of pain, as time from randomization until the first worsening of pain. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of pain were censored at the date of their last MDASI-MPM assessment with a non-missing pain score.
Time Frame
up to approx. 30 months (data cut-off: 31-May-2017)
Title
Percentage of Participants With Confirmed Improvement of Pain
Description
Improvement rate of pain was defined as the number of patients with confirmed improvement of pain (based on the "pain at its worst" item of MDASI-MPM), divided by the number of patients evaluable for improvement of pain.
Time Frame
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Title
Percentage of Participant With Treatment-emergent Adverse Events (TEAEs)
Description
TEAEs were defined as all AEs starting or worsening within the treatment period.
Time Frame
Up to approx. 55 months (data cut-off: 02-Jul-2019) - Time from randomization until 30 days after last treatment (general AEs), or further until death from any cause (selected AEs).
Title
Number of Deaths
Description
TEAE(s) associated with a fatal outcome (CTCAE Grade 5) at the time of the data cut-off 06-Apr-2018.
Time Frame
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Title
Overall Survival (OS) - Addendum
Description
Overall survival (OS) was defined as time from randomization until death from any cause; Only descriptive analyses of OS were repeated in with the data as of the 02 JUL 2019.
Time Frame
Up to approx. 55 month (data cut-off: 02-JUL-2019) - Time from randomization until death from any cause

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-1503
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
Norwich
State/Province
Connecticut
ZIP/Postal Code
06360
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75251
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
City
Woolloogabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5043
Country
Australia
City
Richmond
State/Province
Victoria
ZIP/Postal Code
3122
Country
Australia
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
City
Bruxelles - Brussel
ZIP/Postal Code
1200
Country
Belgium
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Sint-niklaas
ZIP/Postal Code
9100
Country
Belgium
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
City
Helsinki
ZIP/Postal Code
00290
Country
Finland
City
Turku
ZIP/Postal Code
20520
Country
Finland
City
Vaasa
ZIP/Postal Code
65130
Country
Finland
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
City
Caen Cedex 5
ZIP/Postal Code
14076
Country
France
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
City
Marseille
ZIP/Postal Code
13915
Country
France
City
Paris
ZIP/Postal Code
75018
Country
France
City
Paris
ZIP/Postal Code
75020
Country
France
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
City
Pordenone
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33081
Country
Italy
City
Bergamo
State/Province
Lombardia
ZIP/Postal Code
24125
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20089
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Monza Brianza
State/Province
Lombardia
ZIP/Postal Code
20900
Country
Italy
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10043
Country
Italy
City
Siena
State/Province
Toscana
ZIP/Postal Code
53100
Country
Italy
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
City
Krakow
ZIP/Postal Code
31-202
Country
Poland
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
City
Szczecin
ZIP/Postal Code
70-891
Country
Poland
City
Omsk
ZIP/Postal Code
644013
Country
Russian Federation
City
Yekaterinburg
ZIP/Postal Code
620036
Country
Russian Federation
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
City
Alicante
ZIP/Postal Code
03010
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Málaga
ZIP/Postal Code
29010
Country
Spain
City
Adana
ZIP/Postal Code
01330
Country
Turkey
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
City
Eskisehir
ZIP/Postal Code
26480
Country
Turkey
City
Istanbul
ZIP/Postal Code
34899
Country
Turkey
City
Malatya
ZIP/Postal Code
44280
Country
Turkey
City
Yenimahalle
ZIP/Postal Code
06200
Country
Turkey
City
Plymouth
State/Province
Devon
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
City
Maidstone
State/Province
Kent
ZIP/Postal Code
ME16 9QQ
Country
United Kingdom
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35358455
Citation
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.
Results Reference
derived
Links:
URL
https://clinicaltrials.bayer.com/
Description
Click here to find results for studies related to Bayer Healthcare products.

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Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)

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