Clinical Trial Results:
A Phase II Clinical Trial of Pembrolizumab (MK-3475) in Subjects with Advanced/Unresectable or Metastatic Urothelial Cancer
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Summary
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EudraCT number |
2014-002206-20 |
Trial protocol |
ES DK IT IE GB HU NL |
Global end of trial date |
18 Feb 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Feb 2023
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First version publication date |
24 Feb 2023
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Other versions |
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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 |
3475-052
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02335424 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Street LLC
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Sponsor organisation address |
126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Street LLC, ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Street LLC, ClinicalTrialsDisclosure@merck.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 |
18 Feb 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Jun 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Feb 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 |
This is a study using pembrolizumab (MK-3475, KEYTRUDA®) for first-line treatment of participants with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. The primary study objective is to determine the objective response rate (ORR) in all participants and by programmed cell death ligand 1 (PD-L1) status.
With Amendment 4, once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Feb 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Australia: 5
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Country: Number of subjects enrolled |
Canada: 29
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Country: Number of subjects enrolled |
Denmark: 7
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Country: Number of subjects enrolled |
Guatemala: 4
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Country: Number of subjects enrolled |
Hungary: 10
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Country: Number of subjects enrolled |
Ireland: 4
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Country: Number of subjects enrolled |
Israel: 33
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Country: Number of subjects enrolled |
Italy: 16
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Country: Number of subjects enrolled |
Korea, Republic of: 10
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Country: Number of subjects enrolled |
Malaysia: 1
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Country: Number of subjects enrolled |
Netherlands: 5
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Country: Number of subjects enrolled |
Singapore: 4
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Country: Number of subjects enrolled |
Spain: 52
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Country: Number of subjects enrolled |
Taiwan: 5
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Country: Number of subjects enrolled |
United Kingdom: 27
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Country: Number of subjects enrolled |
United States: 162
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Worldwide total number of subjects |
374
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EEA total number of subjects |
94
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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) |
68
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From 65 to 84 years |
265
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85 years and over |
41
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Recruitment
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Recruitment details |
Participants were eligible to receive second course treatment with pembrolizumab if they met criteria for re-treatment. Per protocol, only data generated during the initial course of treatment contributed to efficacy and safety outcome measures. | ||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
The study enrolled 374 participants and 370 participants received ≥1 dose of study treatment. | ||||||||||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
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Arms
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Arm title
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Pembrolizumab 200 mg | ||||||||||||||||||||||||||||
Arm description |
Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
pembrolizumab
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Investigational medicinal product code |
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Other name |
KEYTRUDA®, MK-3475
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
200 mg by intravenous infusion on Day 1 of each 21-day cycle
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Baseline characteristics reporting groups
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Reporting group title |
Pembrolizumab 200 mg
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Reporting group description |
Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pembrolizumab 200 mg
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Reporting group description |
Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year. | ||
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End point title |
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [1] | ||||||||
End point description |
ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
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End point type |
Primary
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End point timeframe |
Up to approximately 80.5 months
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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: There was no statistical analysis planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [2] | ||||||||
End point description |
ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
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End point type |
Primary
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End point timeframe |
Up to approximately 80.5 months
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| Notes [2] - 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: There was no statistical analysis planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [3] | ||||||||
End point description |
ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥10% CPS.
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End point type |
Primary
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End point timeframe |
Up to approximately 80.5 months
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| Notes [3] - 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: There was no statistical analysis planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed by Blinded Independent Central Review (BICR) in All Participants | ||||||||
End point description |
PFS was determined in all participants. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by BICR. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed by BICR in Participants with a PD-L1 CPS of ≥10% | ||||||||
End point description |
DOR was determined in participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 by BICR. DOR was the time from first evidence of CR or PR until PD or death and was calculated using the KM method. Participants who had not progressed or died at the time of analysis were censored at the date of last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the SOD of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. 9999 indicated that the median and upper limit of the 95% CI was not reached at time of data cut-off due to an insufficient number of responding participants with relapse Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment had a PD-L1 positive expression of ≥10% CPS and had a confirmed CR or PR.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed by BICR in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
DOR was determined in participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 by BICR. DOR was the time from first evidence of CR or PR until PD or death and was calculated using the KM method. Participants who had not progressed or died at the time of analysis were censored at the date of last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the SOD of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. 9999 indicated that the upper limit of the 95% CI was not reached at time of data cut-off due to an insufficient number of responding participants with relapse. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment, had a PD-L1 positive expression of ≥1% CPS, and had a confirmed CR or PR.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed by Blinded Independent Central Review (BICR) in All Participants | ||||||||
End point description |
DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR. DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death and was calculated using the product-limit (Kaplan-Meier [KM]) method for censored data. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters (SOD) of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a confirmed CR or PR.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed by BICR in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
PFS was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by BICR. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed by BICR in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | ||||||||
End point description |
PFS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by BICR. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥10% CPS.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) in All Participants | ||||||||
End point description |
OS was determined for all participants and was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
OS was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | ||||||||
End point description |
OS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥10% CPS.
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End point type |
Secondary
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End point timeframe |
Up to approximately 80.5 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival Rate (PFS Rate) at Month 6 As Assessed by BICR in All Participants | ||||||||
End point description |
The PFS rate was determined in all participants at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by BICR. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit (Kaplan-Meier [KM]) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Month 6
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival Rate (PFS Rate) at Month 12 As Assessed by BICR in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by BICR. PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit KM method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
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End point type |
Secondary
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End point timeframe |
Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival Rate (PFS Rate) at Month 12 As Assessed by BICR in All Participants | ||||||||
End point description |
The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by BICR. Per RECIST 1.1, PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum, or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit (Kaplan-Meier [KM]) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
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End point type |
Secondary
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End point timeframe |
Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival Rate (PFS Rate) at Month 6 As Assessed by BICR in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by BICR. PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit KM method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 6
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Progression Free Survival Rate (PFS Rate) at Month 6 As Assessed by BICR in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | ||||||||
End point description |
The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by BICR. PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 6 was calculated using product-limit KM method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥10% CPS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 6
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Progression Free Survival Rate (PFS Rate) at Month 12 As Assessed by BICR in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | ||||||||
End point description |
The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by BICR. PD was a ≥20% increase in the sum of diameters of target lesions plus an absolute increase of ≥5 mm in the sum or the appearance of ≥1 new lesions. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. PFS at Month 12 was calculated using product-limit KM method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥10% CPS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival Rate (OS Rate) at Month 6 in All Participants | ||||||||
End point description |
The OS rate was determined for all participants at Month 6 and was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 6
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival Rate (OS Rate) at Month 6 in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 6
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival Rate (OS Rate) at Month 12 in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | ||||||||
End point description |
The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival Rate (OS Rate) at Month 12 in All Participants | ||||||||
End point description |
The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival Rate (OS Rate) at Month 12 in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. OS at Month 12 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall Survival Rate (OS Rate) at Month 6 in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | ||||||||
End point description |
The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. OS at Month 6 was calculated using product-limit (Kaplan-Meier) method for censored data. Participants were censored at the date of their last assessment. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥10% CPS.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Month 6
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||
End point title |
Number of Participants Who Experienced At Least One Adverse Event (AE) | ||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Up to approximately 80.5 months
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||
End point title |
Programmed Cell Death Ligand 1 (PD-L1) Expression Status | ||||||||||||||
End point description |
PD-L1 expression status was determined as the percent of disease tumor cells, from newly obtained tumor biopsies, demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. The assay uses a Combined Positive Score (CPS) as a measure of PD-L1 positivity. The CPS is calculated as the number of PD-L1-positive cells divided by the number of viable tumor cells analyzed multiplied by 100. A CPS of <1%=negative; ≥1%=positive; and ≥10%=strongly positive. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 1
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||
End point title |
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | ||||||
End point description |
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Up to approximately 26 months
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||
End point title |
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% | ||||||||
End point description |
ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥10% CPS.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Up to approximately 80.5 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) in Participants with a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% | ||||||||
End point description |
ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Up to approximately 80.5 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) in All Participants | ||||||||
End point description |
ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis. The analysis included all participants that received ≥1 dose of study treatment.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Up to approximately 80.5 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to approximately 80.5 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
AEs=all participants who received ≥1 dose of study treatment; all-cause mortality=all allocated participants. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. MedDRA preferred terms "Neoplasm progression (NP)", "Malignant NP" & "Disease progression" not related to study drug are excluded as AEs.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Second Course Pembrolizumab
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Reporting group description |
Participants who met the criteria for retreatment received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle for up to 1 year of treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pembrolizumab
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Reporting group description |
Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to an additional year. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 Oct 2014 |
Amendment 1 revised text in the inclusion criteria section to clearly state that participants must be refractory to available or standard therapy for treatment of their bladder cancer to participate in the biomarker cut-point determination part of the study if they do not meet cisplatin-ineligible criteria. The amendment also revised the safety and tolerability objective to state that safety and tolerability will be evaluated in all subjects regardless of programmed cell death ligand 1(PD-L1) status. |
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16 Mar 2016 |
Amendment 2 added objectives for programmed cell death ligand 1 (PD-L1) positive and PD-L1 strongly positive populations and removed hypotheses testing. Revisions were made to the statistical methods to adjust for the removal of the hypotheses testing. |
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19 Dec 2017 |
Amendment 3 added guidelines for dose modification in the event of myocarditis and updated guidelines for several other conditions. |
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20 Sep 2019 |
Amendment 4 added language regarding the potential for participants to be enrolled in an extension study if one becomes available. |
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21 May 2021 |
Amendment 5 updated the dose modification and toxicity management guidelines for immune-related adverse events (irAEs). |
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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 | |||
