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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03840902




Registration number
NCT03840902
Ethics application status
Date submitted
12/02/2019
Date registered
15/02/2019

Titles & IDs
Public title
M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)
Scientific title
A Multicenter, Double Blind, Randomized, Controlled Study of M7824 With Concurrent Chemoradiation Followed by M7824 Versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants With Unresectable Stage III Non-small Cell Lung Cancer
Secondary ID [1] 0 0
2018-003265-34
Secondary ID [2] 0 0
MS200647_0005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - M7824
Treatment: Drugs - Placebo
Treatment: Drugs - Durvalumab
Treatment: Drugs - Etoposide
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Carboplatin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cisplatin
Treatment: Other - Intensity Modulated Radiation Therapy (IMRT)

Experimental: cCRT plus M7824 followed by M7824 - Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824.

Active comparator: cCRT plus placebo followed by durvalumab - Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with placebo matched to M7824 followed by durvalumab.


Treatment: Drugs: M7824
Participants received intravenous infusion of 1200 milligram (mg) M7824 over 1 hour every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

Treatment: Drugs: Placebo
Participants received intravenous infusion of placebo matched to M7824 over 1 hour q2w during cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

Treatment: Drugs: Durvalumab
Participants received intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) over 1 hour q2w up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

Treatment: Drugs: Etoposide
Participants received etoposide 50 mg/m\^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT.

Treatment: Drugs: Pemetrexed
Participants received pemetrexed at a dose of 500 mg/m\^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT.

Treatment: Drugs: Carboplatin
Participants received carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.

Treatment: Drugs: Paclitaxel
Participants received paclitaxel intravenously at a dose of 45 mg/m\^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.

Treatment: Drugs: Cisplatin
In combination with etoposide, participants received cisplatin 50 mg/m\^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants received cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT.

Treatment: Other: Intensity Modulated Radiation Therapy (IMRT)
Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray \[Gy\]).
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
Timepoint [1] 0 0
Time from randomization to the date of first documentation of PD or death, assessed approximately up to 27 months
Secondary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events
Timepoint [1] 0 0
Time from randomization up to data cut off (assessed up to 27 months)
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Time from randomization to the date of death due to any cause, assessed up to 27 months
Secondary outcome [3] 0 0
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
Timepoint [3] 0 0
Time from randomization up to data cut off (assessed up to 27 months)
Secondary outcome [4] 0 0
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
Timepoint [4] 0 0
Time from first documentation of objective response to the date of first documentation of PD or death due to any cause, assessed approximately up to 27 months
Secondary outcome [5] 0 0
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of M7824
Timepoint [5] 0 0
Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
Secondary outcome [6] 0 0
Serum Concentration Immediately Before Next Dosing (Ctrough) of M7824
Timepoint [6] 0 0
Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
Secondary outcome [7] 0 0
Number of Participants With Positive Antidrug Antibodies (ADA)
Timepoint [7] 0 0
Time from randomization up to data cut off (assessed up to 27 months)

Eligibility
Key inclusion criteria
* Participants must have histologically documented NSCLC who present with Stage III locally advanced, unresectable disease (International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
* Participants with tumor harboring an Epidermal growth factor receptor (EGFR) sensitizing (activating) mutation, Anaplastic lymphoma kinase (ALK) translocation, ROS-1 rearrangement are eligible.
* Participants must have adequate pulmonary function defined as a forced expiratory volume in 1 second (FEV1) greater than equals to (>=) 1.2 liters or >= 50% of predicted normal volume measured within 3 weeks prior to randomization.
* Adequate hematological, hepatic and renal function as defined in the protocol
* Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participants with Mixed small cell with non-small cell lung cancer histology
* Recent major surgery within 4 weeks prior to entry into the study
* Significant acute or chronic infections including human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome, Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and active tuberculosis
* Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization
* Active autoimmune disease that has required systemic treatment in past 1 year (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
* Any prior systemic cytotoxic chemotherapy for their NSCLC or any antibody or drug targeting T-cell coregulatory proteins

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/04/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/02/2023
Sample size
Target
Accrual to date
Final
153
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Bendigo Hospital - Bendigo
Recruitment hospital [2] 0 0
The Townsville Hospital - Douglas
Recruitment hospital [3] 0 0
Calvary Central Districts Hospital - Elizabeth Vale
Recruitment hospital [4] 0 0
St Vincent's Hospital Melbourne - PARENT - Fitzroy
Recruitment hospital [5] 0 0
University Hospital Geelong - PARENT - Geelong
Recruitment hospital [6] 0 0
Austin Health - Heidelberg Heights
Recruitment hospital [7] 0 0
Centro de Investigacion Pergamino SA - Pergamino
Recruitment hospital [8] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [9] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [10] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [11] 0 0
South West Healthcare - South West Oncology - Warrnambool
Recruitment postcode(s) [1] 0 0
- Bendigo
Recruitment postcode(s) [2] 0 0
- Douglas
Recruitment postcode(s) [3] 0 0
- Elizabeth Vale
Recruitment postcode(s) [4] 0 0
- Fitzroy
Recruitment postcode(s) [5] 0 0
- Geelong
Recruitment postcode(s) [6] 0 0
- Heidelberg Heights
Recruitment postcode(s) [7] 0 0
- Pergamino
Recruitment postcode(s) [8] 0 0
- Randwick
Recruitment postcode(s) [9] 0 0
- St Albans
Recruitment postcode(s) [10] 0 0
- St Leonards
Recruitment postcode(s) [11] 0 0
- Warrnambool
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Argentina
State/province [16] 0 0
Cordoba
Country [17] 0 0
Argentina
State/province [17] 0 0
San Juan
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Belgium
State/province [19] 0 0
Namur
Country [20] 0 0
Belgium
State/province [20] 0 0
Roeselare
Country [21] 0 0
Belgium
State/province [21] 0 0
Yvoir
Country [22] 0 0
Brazil
State/province [22] 0 0
Barretos
Country [23] 0 0
Brazil
State/province [23] 0 0
Itajaí
Country [24] 0 0
Brazil
State/province [24] 0 0
Porto Alegre
Country [25] 0 0
Brazil
State/province [25] 0 0
Rio de Janeiro
Country [26] 0 0
Brazil
State/province [26] 0 0
São Paulo
Country [27] 0 0
Canada
State/province [27] 0 0
Kelowna
Country [28] 0 0
China
State/province [28] 0 0
Beijing
Country [29] 0 0
China
State/province [29] 0 0
Changchun
Country [30] 0 0
China
State/province [30] 0 0
Hangzhou
Country [31] 0 0
Czechia
State/province [31] 0 0
Olomouc
Country [32] 0 0
France
State/province [32] 0 0
Bayonne
Country [33] 0 0
France
State/province [33] 0 0
Marseille cedex 20
Country [34] 0 0
France
State/province [34] 0 0
Paris Cedex 05
Country [35] 0 0
France
State/province [35] 0 0
Saint Herblain
Country [36] 0 0
Germany
State/province [36] 0 0
Hamburg
Country [37] 0 0
Germany
State/province [37] 0 0
Oldenburg
Country [38] 0 0
Japan
State/province [38] 0 0
Bunkyo-ku
Country [39] 0 0
Japan
State/province [39] 0 0
Hidaka-shi
Country [40] 0 0
Japan
State/province [40] 0 0
Kashiwa-shi
Country [41] 0 0
Japan
State/province [41] 0 0
Kobe-shi
Country [42] 0 0
Japan
State/province [42] 0 0
Koto-ku
Country [43] 0 0
Japan
State/province [43] 0 0
Kurume-shi
Country [44] 0 0
Japan
State/province [44] 0 0
Nagoya-shi
Country [45] 0 0
Japan
State/province [45] 0 0
Osaka-shi
Country [46] 0 0
Japan
State/province [46] 0 0
Osakasayama-shi
Country [47] 0 0
Japan
State/province [47] 0 0
Sunto-gun
Country [48] 0 0
Japan
State/province [48] 0 0
Yokohama-shi
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Daegu
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Seongnam
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Seoul
Country [52] 0 0
Netherlands
State/province [52] 0 0
's Hertogenbosch
Country [53] 0 0
Netherlands
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Amersfoort
Country [54] 0 0
Netherlands
State/province [54] 0 0
Breda
Country [55] 0 0
Netherlands
State/province [55] 0 0
Groningen
Country [56] 0 0
Netherlands
State/province [56] 0 0
Harderwijk
Country [57] 0 0
Netherlands
State/province [57] 0 0
Nieuwegein
Country [58] 0 0
Netherlands
State/province [58] 0 0
Tilburg
Country [59] 0 0
Netherlands
State/province [59] 0 0
Zwolle
Country [60] 0 0
Spain
State/province [60] 0 0
Barcelona
Country [61] 0 0
Spain
State/province [61] 0 0
L'Hospitalet de Llobregat
Country [62] 0 0
Spain
State/province [62] 0 0
Madrid
Country [63] 0 0
Spain
State/province [63] 0 0
Majadahonda
Country [64] 0 0
Spain
State/province [64] 0 0
Málaga
Country [65] 0 0
Spain
State/province [65] 0 0
Pamplona
Country [66] 0 0
Spain
State/province [66] 0 0
Santiago de Compostela
Country [67] 0 0
Spain
State/province [67] 0 0
Sevilla
Country [68] 0 0
Spain
State/province [68] 0 0
Valencia
Country [69] 0 0
Spain
State/province [69] 0 0
Vigo
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taichung
Country [71] 0 0
Taiwan
State/province [71] 0 0
Tainan
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Available to whom?
Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://bit.ly/IPD21


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03840902