Clinical Trial Results:
A Phase II, Multicenter, Open-label Study to Investigate the Clinical Efficacy of M7824 Monotherapy in Participants With Locally Advanced or Metastatic Biliary Tract Cancer Who Fail or Are Intolerant to First-line Platinum-Based Chemotherapy
Summary
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EudraCT number |
2018-003707-19 |
Trial protocol |
FR DE GB ES IT |
Global end of trial date |
30 Sep 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Oct 2023
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First version publication date |
01 Oct 2023
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MS200647_0047
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03833661 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Merck Healthcare KGaA, Darmstadt, Germany
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Sponsor organisation address |
Frankfurter Strasse 250, Darmstadt, Germany, 64293
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Public contact |
Communication Centre, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
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Scientific contact |
Communication Centre, Merck Healthcare KGaA, Darmstadt, Germany, +49 6151725200, service@merckgroup.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Sep 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Sep 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study was to evaluate M7824 monotherapy in subjects with advanced or metastatic biliary tract cancer (BTC) who failed or were intolerant to first-line (1L) chemotherapy.
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Protection of trial subjects |
Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Mar 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 23
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Country: Number of subjects enrolled |
France: 15
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Country: Number of subjects enrolled |
Spain: 17
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Country: Number of subjects enrolled |
Italy: 19
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Germany: 9
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Country: Number of subjects enrolled |
Japan: 21
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Country: Number of subjects enrolled |
Korea, Republic of: 34
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Country: Number of subjects enrolled |
China: 11
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Country: Number of subjects enrolled |
Taiwan: 9
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Worldwide total number of subjects |
159
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EEA total number of subjects |
60
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
76
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From 65 to 84 years |
83
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
Pre-assignment
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Screening details |
First subject signed informed consent: 26 Mar 2019, Clinical cutoff date: 30 March 2021. | ||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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M7824 | ||||||
Arm description |
Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
M7824
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Investigational medicinal product code |
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Other name |
Bintrafusp alfa
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
M7824 administered to subjects at a dose of 1200 mg once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
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Baseline characteristics reporting groups
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Reporting group title |
M7824
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Reporting group description |
Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
M7824
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Reporting group description |
Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal. |
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End point title |
Percentage of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) [1] | ||||||||
End point description |
Confirmed objective response was defined as the percentage of subjects with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC. Intention-To-Treat (ITT) analysis set included all subjects who were administered at least one dose of M7824.
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End point type |
Primary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical and comparison analysis were performed in single arm for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | ||||||||||||||||||
End point description |
Adverse Event (AE) was defined any untoward medical occurrence in a subject administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention. AESIs included Infusion-related reactions, Immune-related AEs, Transforming growth factor-beta (TGF-β) inhibition mediated skin AE and anemia. Safety analysis set included all subjects who were administered at least one dose of M7824.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Durable Response Rate (DRR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) | ||||||||
End point description |
DRR was defined as the percentage of subjects with confirmed objective response (CR or PR) with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DRR was determined according to RECIST v1.1 and assessed by IRC. ITT analysis set included all subjects who were administered at least one dose of M7824. Here, "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) | ||||||||
End point description |
DOR was defined for subjects with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates. ITT analysis set was used. "Number of Subjects Analyzed" = subjects who were evaluable for this endpoint. "99.9" = The upper limit could not be estimated due to insufficient number of events by the date of data cutoff.
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End point type |
Secondary
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End point timeframe |
Time from first documentation of objective response to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator | ||||||||
End point description |
Confirmed objective response was defined as the percentage of subjects with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by Investigator. ITT analysis set included all subjects who were administered at least one dose of M7824.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC) | ||||||||
End point description |
PFS was defined as the time from first administration of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. ITT analysis set included all subjects who were administered at least one dose of M7824.
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End point type |
Secondary
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End point timeframe |
Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (736 days)
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No statistical analyses for this end point |
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End point title |
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator | ||||||||
End point description |
DOR was defined for subjects with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and assessed by Investigator. Results were calculated based on Kaplan-Meier estimates. ITT analysis set included all subjects who were administered at least one dose of M7824. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Time from first documentation of objective response to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Durable Response Rate (DRR) Acoording to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator | ||||||||
End point description |
DRR was defined as the percentage of subjects with confirmed objective response (CR or PR) with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DRR was determined according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and assessed by Investigator. ITT analysis set included all subjects who were administered at least one dose of M7824. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator | ||||||||
End point description |
PFS was defined as the time from first administration of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. ITT analysis set included all subjects who were administered at least one dose of M7824.
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End point type |
Secondary
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End point timeframe |
Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (736 days)
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No statistical analyses for this end point |
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End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method. ITT analysis set included all subjects who were administered at least one dose of M7824.
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End point type |
Secondary
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End point timeframe |
Time from first administration of study drug to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Serum Pre-Dose Concentrations (Ctrough) of M7824 | ||||||||||||||||||||||||||||
End point description |
Ctrough was defined as the concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing). Pharmacokinetic (PK) analysis set included all subjects who completed at least one dose of M7824 and who provided at least one sample with a measurable concentration of M7824. Here, "Number of subjects Analyzed" signifies those subjects who were evaluable for this endpoint and "n" signifies those participants who were evaluable at specified time points for this endpoint. Here, "9999"=Geometric Mean and Geometric Coefficient of Variation were not calculated if fewer than 3 subjects have reportable parameter values.
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End point type |
Secondary
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End point timeframe |
At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421 and Day 505
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No statistical analyses for this end point |
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End point title |
Number of Subjects with Positive Antidrug Antibodies (ADA) | ||||||
End point description |
Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of subjects with positive ADA were reported. Immunogenicity analysis set included all subjects who received at least one dose of M7824 and who had at least one valid result of ADA.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Serum Concentration at End of Infusion (CEOI) of M7824 | ||||||||||||
End point description |
Serum Concentration at End of Infusion (CEOI) of M7824 is reported. Pharmacokinetic (PK) analysis set included all subjects who completed at least one dose of M7824 and who provided at least one sample with a measurable concentration of M7824. Here, "Number of subjects Analyzed" signifies those subjects who were evaluable for this endpoint and "n" signifies those subjects who were evaluable at specified time points for this endpoint.
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End point type |
Secondary
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End point timeframe |
At Day 1 and Day 29
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression | ||||||||||||||||||||||||||||||||||||||||
End point description |
Confirmed objective response: percentage of subjects with a confirmed objective response of CR or PR. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup: PD-L1 expression on tumor cells (TC) and on immune cells (IC) at baseline and in the following categories: <1%, >=1%, <5%, >=5%, <25%, >=25%, <50%, >=50% were reported. ITT analysis set was used. "Number of Subjects Analyzed" = subjects who were evaluable for this endpoint and "n" = subjects who were evaluable for the specified categories for this endpoint.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Confirmed Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) According to Microsatellite instability (MSI) Status | ||||||||||||||
End point description |
Confirmed OR: percentage of subjects with a confirmed OR of CR or PR.Confirmed CR: at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR: at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed OR was adjudicated by IRC through MSI Status subgroups as:- MSI High = if subject is MSI High for any (at least one) test;- Microsatellite stable (MSS) or MSI Low = if subject is not MSI High for any test;- Unknown (missing) = no MSI tests available at baseline was reported. MSI high: if 2 or more unstable markers were detected in sample; MSI low: if 1 marker was unstable and remaining markers were stable and MSS if all markers were stable. ITT analysis set was used. "Number of Subjects Analyzed"=subjects who were evaluable for this endpoint and "n"=subjects who were evaluable for the specified categories for this endpoint. "99999" = None of subjects were evaluable for specified category.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression | ||||||||||||||||||||||||||||||||||||||||
End point description |
DOR: subjects with confirmed response, as time from first documentation of objective response (CR/PR) to date of first documentation of PD/death due to any cause, whichever occurred first. PD: At least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was adjudicated by IRC through PD-L1 Subgroup: PD-L1 expression on tumor cells (TC) and on immune cells (IC) at baseline and in following categories: <1%, >=1%, <5%, >=5%, <25%, >=25%, <50%, >=50% was reported. ITT analysis set was used. "Number of Subjects Analyzed" =subjects who were evaluable for this endpoint; "n"=subjects who were evaluable for the specified categories for this endpoint. "999" = Due to small number of events, Median and Upper limit of 95% Confidence Interval could not derive and "99999" = None of the subjects were evaluable for the specified category.
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End point type |
Secondary
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End point timeframe |
Time from first documentation of objective response to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to According to Microsatellite instability (MSI) Status | ||||||||||||||
End point description |
DOR: participants with confirmed response, as the time from first documentation of objective response (CR/PR) to the date of first documentation of PD or death due to any cause, whichever occurred first.PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was by IRC through MSI Status subgroups as:- MSI High = if subject is MSI High for any (at least one) test;- MSS or MSI Low = if subject is not MSI High for any test;- Unknown (missing) = no MSI tests available at baseline was reported. ITT analysis set was used. "Number of Subjects Analyzed" =subjects who were evaluable for this endpoint and "n"= subjects who were evaluable for the specified categories for this endpoint. "999" = Due to small number of events, Median and Upper limit of 95% Confidence Interval could not derive and "99999" = None of the subjects were evaluable for the specified category.
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End point type |
Secondary
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End point timeframe |
Time from first documentation of objective response to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Durable Response Rate (DRR) as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression | ||||||||||||||||||||||||||||||||||||||||
End point description |
DRR was defined as the percentage of subjects with confirmed objective response (CR or PR) with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DRR was determined according to RECIST v1.1 and adjudicated by IRC through PD-L1 Subgroup: PD-L1 expression on tumor cells (TC) and on immune cells (IC) at baseline and in the following categories: <1%, >=1%, <5%, >=5%, <25%, >=25%, <50%, >=50% was reported. ITT analysis set was used. "Number of Subjects Analyzed" =subjects who were evaluable for this endpoint and "n" signifies those subjects who were evaluable for the specified categories for this endpoint.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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End point title |
Durable Response Rate (DRR) as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by an Independent Review Committee (IRC) According to According to Microsatellite instability (MSI) Status | ||||||||||||||
End point description |
DRR: percentage of subjects with confirmed OR (CR/PR) with duration of at least 6 months. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DRR was determined according to RECIST v1.1 and adjudicated by IRC through MSI Status subgroups as:- MSI High = if subject is MSI High for any (at least one) test;- MSS or MSI Low = if subject is not MSI High for any test;- Unknown (missing) = no MSI tests available at baseline was reported. ITT analysis set included all subjects who were administered at least one dose of M7824. Here, "Number of Subjects Analyzed" signifies those subjects who were evaluable for this endpoint and "n" signifies those subjects who were evaluable for the specified categories for this endpoint. Here, "99999" = None of subjects were evaluable for specified category.
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End point type |
Secondary
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End point timeframe |
Time from first treatment to data cutoff (assessed up to 736 days)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Time from first treatment to data cutoff (assessed up to 736 days)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
M7824
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Reporting group description |
Subjects received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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26 Aug 2019 |
• To clarify eligibility criteria of the study population.
• To modify non-serious adverse event of special interest (AESI) reporting.
• To include separate consent forms for treatment after initial and confirmed progressive disease.
• To revise the laboratory assessments.
• To include exploratory analysis of tumor shrinkage per biliary tract cancer (BTC) subtype. |
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10 Oct 2019 |
To clarify exclusion criteria of the study population and the management of immune-related adverse event and bleeding events during study intervention. |
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20 Oct 2020 |
• Provide sufficient survival follow up data collection for participants with long-term benefit.
• Minor text revisions are made for clarity, readability, consistency of language across the development program, and compliance with current Sponsor guidelines. |
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22 Jun 2021 |
• The risk reclassification was based on in-depth analysis of a pooled safety dataset of N = 765 subjects who received M7824 monotherapy at 1200 mg Q2W. The information on the number of subjects treated with M7824 is provided in the IB.
• Infusion-related reactions are reclassified from “important identified risk” to “identified risk” for M7824.
• Skin Adverse Events have been renamed to TGF-β Inhibition Mediated Skin Reactions.
• Term “treatment-related anemia events” has been revised to “anemia” and reclassified from “important potential risk” to “important identified risk” for M7824.
• Bleeding events are reclassified from “potential risk” to “important identified risk” for M7824. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |