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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000294-13 | EudraCT Number | ||
| 152987 | Registry Identifier | JAPIC |
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This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC). Part 1 of the study will examine the efficacy and safety of pembrolizumab monotherapy as first line or above treatment in participants who have received either no prior systemic treatment or at least one prior systemic treatment for metastatic breast cancer. Part 2 of the study, if done, will expand the investigation of pembrolizumab treatment in a subgroup of participants from Part 1 and will only start after enrollment in Part 1 has been completed. There will be no hypothesis testing in this study.
Qualified participants who complete up to ~2 years of pembrolizumab treatment but progress after discontinuation may be eligible for a second course of pembrolizumab for up to ~1 additional year, at the Investigator's discretion. Per protocol, response or progression during this second course will not count towards efficacy outcome measure and adverse events during this second course will not count towards safety outcome measures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: Pembrolizumab | Experimental | Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants will be administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~ 2 years). |
|
| Cohort B: Pembrolizumab | Experimental | Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants will be administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~ 2 years). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Biological | IV infusion of 200 mg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Central Imaging Vendor (CIV) in All Cohort A Participants | ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in sum of diameters [SOD] of target lesions) per RECIST 1.1 by CIV. ORR was estimated by Agresti-Coull (A-C) method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, for all participants in Cohort A. Per protocol final ORR analysis in all Cohort A participants was done at the time of final statistical efficacy analysis, with a 10-November (Nov)-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was planned and conducted as a pre-specified primary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| ORR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With Programmed Cell Death- Ligand 1 (PD-L1) Positive Tumor Expression | ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for the subgroup of Cohort A participants with tumor immunohistochemistry (IHC) defined-PD-L1 positive expression (PD-L1+). Per protocol final ORR analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| Number of Participants Who Experienced at Least One Adverse Event (AE) |
| Measure | Description | Time Frame |
|---|---|---|
| ORR Per RECIST 1.1 by CIV in All Cohort B Participants | ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for all participants in Cohort B. Per protocol final ORR analysis in all Cohort B participants was done at the time of final statistical efficacy analysis, with a 10-Nov-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was planned and conducted as a pre-specified secondary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was analyzed separately as a pre-specified primary outcome analysis and reported earlier in the record. |
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Inclusion Criteria:
For the purposes of this study, neoadjuvant and/or adjuvant chemotherapy regimens do not count as a prior line of therapy.
For second line plus monotherapy (Parts 1 and 2):
For first line monotherapy (Part 1):
For second line plus monotherapy (Part 2):
- Has PD-L1 strong positive mTNBC
For all parts:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37099733 | Derived | Loi S, Salgado R, Schmid P, Cortes J, Cescon DW, Winer EP, Toppmeyer DL, Rugo HS, De Laurentiis M, Nanda R, Iwata H, Awada A, Tan AR, Sun Y, Karantza V, Wang A, Huang L, Saadatpour A, Cristescu R, Yearley J, Lunceford J, Jelinic P, Adams S. Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. JCO Precis Oncol. 2023 Apr;7:e2200317. doi: 10.1200/PO.22.00317. | |
| 35101941 |
| Label | URL |
|---|---|
| Merck Oncology Clinical Trial Information | View source |
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Per protocol, response or progression during the second pembrolizumab course was not counted towards efficacy outcome measures, and adverse events during the second pembrolizumab course were not counted towards safety outcome measures.
Based on protocol-specified inclusion criteria and outcome analyses requirements, Part 2 was not conducted.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A: Pembrolizumab | Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year). |
| FG001 | Cohort B: Pembrolizumab | Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A: Pembrolizumab | Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Central Imaging Vendor (CIV) in All Cohort A Participants | ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in sum of diameters [SOD] of target lesions) per RECIST 1.1 by CIV. ORR was estimated by Agresti-Coull (A-C) method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, for all participants in Cohort A. Per protocol final ORR analysis in all Cohort A participants was done at the time of final statistical efficacy analysis, with a 10-November (Nov)-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was planned and conducted as a pre-specified primary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record. | Per protocol ORR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A who got ≥1 dose of study drug. Per protocol ORR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants as a pre-specified secondary outcome analysis and is not included in this analysis. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
Safety: Up to ~31 months for pembrolizumab first course and up to additional ~15 months for pembrolizumab second course (AEs were collected through 90 days post treatment for SAEs and 30 days post treatment for NSAEs); All-cause mortality (ACM): Up to ~54 months for pembrolizumab first and second course
Safety and ACM were analyzed by Cohort (A and B) and by Course of pembrolizumab (first and second course) in all participants who got ≥1 dose of study drug, and were assessed from a participant's enrolment/treatment initiation. Per protocol disease progression of cancer was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A: Pembrolizumab First Course | Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants were administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 8, 2017 | Nov 18, 2020 | Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who experienced at least one AE, for the first pembrolizumab course, was assessed from enrollment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug. |
| Up to ~31 months |
| Number of Participants Who Discontinued Study Drug Due to an AE | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who discontinued study drug due to an AE, in the first pembrolizumab course, was assessed from enrolment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug. | Up to ~31 months |
| Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| Duration of Response (DOR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants | For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until progressive disease (PD: ≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by Kaplan-Meier (KM) method and analyzed by cohort is reported here for all participants in Cohort A and Cohort B who had CR or PR per RECIST 1.1 by CIV. Per protocol final DOR analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| DOR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until PD (≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by KM method and analyzed by Cohort is reported here for subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+) and CR/PR per RECIST 1.1 by CIV. Per protocol final DOR analysis in Cohort A PD-L1+ subgroup was done at time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and DOR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| Disease Control Rate (DCR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants | DCR was defined as the percentage of participants in the analysis population who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD [≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR, for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyzed by Cohort, for all participants in Cohort A and Cohort B. Per protocol final DCR analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis, with a 10-Nov-2017 cutoff. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| DCR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | DCR was defined as the percentage of participants who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD [≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyzed by Cohort for subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final DCR analysis in Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and DCR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| Progression Free Survival (PFS) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants | PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final PFS analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. | Up to ~28 months (through pre-specified final statistical analysis cut-off date of 10-Nov-2017) |
| PFS Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for the subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final PFS analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and PFS per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| Overall Survival (OS) in All Cohort A and Cohort B Participants | OS was defined as the time from the first dose of study drug to death due to any cause. OS was estimated by KM method. Per protocol OS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final OS analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| OS in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | OS was defined as the time from the first dose of study drug to death due to any cause. OS was estimated by KM method. Per protocol OS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, is reported here for the subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final OS analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and OS in all Cohort B participants was analyzed separately and reported earlier in the record. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| Odds Ratio of Association Between PD-L1 Tumor Expression and Objective Response (OR) Per RECIST 1.1 by CIV in Cohort A Participants | OR comprises CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV. PD-L1 expression is assessed by IHC-defined combined positive score (CPS). Association between (b/w) PD-L1 CPS and OR was assessed by odds ratio using a logistic regression model and was calculated as ratio of odds of OR per unit CPS increase in a single arm (odds ratio=1: no association; odds ratio<1: negative association [increase in CPS lowers odds of OR]; odds ratio >1: positive association [increase in CPS raises odds of OR]). Per protocol odds ratio, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here in a single arm of Cohort A participants with PD-L1 CPS available. Per protocol odds ratio was analyzed at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol odds ratio of association b/w PD-L1 expression and OR was not planned or done in Cohort B participants. | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
| Derived |
| Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091. |
| 30475950 | Derived | Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O'Shaughnessy J, Loi S, Paluch-Shimon S, Tan AR, Card D, Zhao J, Karantza V, Cortes J. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):397-404. doi: 10.1093/annonc/mdy517. |
| 30475947 | Derived | Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):405-411. doi: 10.1093/annonc/mdy518. |
| 27138582 | Derived | Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016 Jul 20;34(21):2460-7. doi: 10.1200/JCO.2015.64.8931. Epub 2016 May 2. |
| Physician Decision |
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| Withdrawal by Subject |
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| Sponsor Decision |
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| Progressive Disease |
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| Lost to Follow-up |
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| Death |
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| BG001 | Cohort B: Pembrolizumab | Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). Qualified participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle (Q3W), for up to 17 cycles (up to ~1 year). |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
|
| Primary | ORR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With Programmed Cell Death- Ligand 1 (PD-L1) Positive Tumor Expression | ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for the subgroup of Cohort A participants with tumor immunohistochemistry (IHC) defined-PD-L1 positive expression (PD-L1+). Per protocol final ORR analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record. | Per protocol ORR for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol ORR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants as a pre-specified secondary outcome analysis and is not included in this analysis. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Primary | Number of Participants Who Experienced at Least One Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who experienced at least one AE, for the first pembrolizumab course, was assessed from enrollment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug. | Per protocol participants who experienced AEs, for the first pembrolizumab course, were analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug. | Posted | Count of Participants | Participants | Up to ~31 months |
|
|
|
| Primary | Number of Participants Who Discontinued Study Drug Due to an AE | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who discontinued study drug due to an AE, in the first pembrolizumab course, was assessed from enrolment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug. | Per protocol participants who discontinued study drug due to an AE, for the first pembrolizumab course, were analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug. | Posted | Count of Participants | Participants | Up to ~31 months |
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|
|
| Secondary | ORR Per RECIST 1.1 by CIV in All Cohort B Participants | ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for all participants in Cohort B. Per protocol final ORR analysis in all Cohort B participants was done at the time of final statistical efficacy analysis, with a 10-Nov-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was planned and conducted as a pre-specified secondary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was analyzed separately as a pre-specified primary outcome analysis and reported earlier in the record. | Per protocol ORR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort B who got ≥1 dose of study drug. Per protocol ORR per RECIST 1.1 by CIV was analyzed separately in all Cohort A participants as a pre-specified primary outcome analysis and is not included in this analysis. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | Duration of Response (DOR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants | For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until progressive disease (PD: ≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by Kaplan-Meier (KM) method and analyzed by cohort is reported here for all participants in Cohort A and Cohort B who had CR or PR per RECIST 1.1 by CIV. Per protocol final DOR analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. | Per protocol DOR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who had CR or PR per RECIST 1.1 by CIV and got ≥1 dose of study drug. | Posted | Median | Full Range | Months | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | DOR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until PD (≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by KM method and analyzed by Cohort is reported here for subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+) and CR/PR per RECIST 1.1 by CIV. Per protocol final DOR analysis in Cohort A PD-L1+ subgroup was done at time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and DOR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record | Per protocol DOR, for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+, had CR or PR per RECIST 1.1 by CIV and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol DOR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants and is not included in this analysis. | Posted | Median | Full Range | Months | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | Disease Control Rate (DCR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants | DCR was defined as the percentage of participants in the analysis population who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD [≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR, for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyzed by Cohort, for all participants in Cohort A and Cohort B. Per protocol final DCR analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis, with a 10-Nov-2017 cutoff. | Per protocol DCR, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | DCR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | DCR was defined as the percentage of participants who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD [≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyzed by Cohort for subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final DCR analysis in Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and DCR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record. | Per protocol DCR, for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol DCR per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants and is not included in this analysis. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | Progression Free Survival (PFS) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants | PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final PFS analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. | Per protocol PFS, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug. | Posted | Median | 95% Confidence Interval | Months | Up to ~28 months (through pre-specified final statistical analysis cut-off date of 10-Nov-2017) |
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|
|
| Secondary | PFS Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for the subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final PFS analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and PFS per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately and reported earlier in the record. | Per protocol PFS, for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol PFS per RECIST 1.1 by CIV was analyzed separately in all Cohort B participants and is not included in this analysis. | Posted | Median | 95% Confidence Interval | Months | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | Overall Survival (OS) in All Cohort A and Cohort B Participants | OS was defined as the time from the first dose of study drug to death due to any cause. OS was estimated by KM method. Per protocol OS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final OS analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. | Per protocol OS, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A and Cohort B who got ≥1 dose of study drug. | Posted | Median | 95% Confidence Interval | Months | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | OS in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression | OS was defined as the time from the first dose of study drug to death due to any cause. OS was estimated by KM method. Per protocol OS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, is reported here for the subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final OS analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and OS in all Cohort B participants was analyzed separately and reported earlier in the record. | Per protocol OS for the first pembrolizumab course, was analyzed by Cohort in the subgroup of Cohort A participants who were PD-L1+ and got ≥1 dose of study drug. Per protocol all Cohort B participants were PD-L1+; per protocol OS was analyzed separately in all Cohort B participants and is not included in this analysis. | Posted | Median | 95% Confidence Interval | Months | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| Secondary | Odds Ratio of Association Between PD-L1 Tumor Expression and Objective Response (OR) Per RECIST 1.1 by CIV in Cohort A Participants | OR comprises CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV. PD-L1 expression is assessed by IHC-defined combined positive score (CPS). Association between (b/w) PD-L1 CPS and OR was assessed by odds ratio using a logistic regression model and was calculated as ratio of odds of OR per unit CPS increase in a single arm (odds ratio=1: no association; odds ratio<1: negative association [increase in CPS lowers odds of OR]; odds ratio >1: positive association [increase in CPS raises odds of OR]). Per protocol odds ratio, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here in a single arm of Cohort A participants with PD-L1 CPS available. Per protocol odds ratio was analyzed at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol odds ratio of association b/w PD-L1 expression and OR was not planned or done in Cohort B participants. | Per protocol odds ratio, for the first pembrolizumab course, was analyzed by Cohort in all participants in Cohort A who got ≥1 dose of study drug and had CPS for PD-L1 available. Per protocol odds ratio of association b/w PD-L1 expression and OR was not planned or conducted in cohort B participants. | Posted | Number | 95% Confidence Interval | Odds Ratio | Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017) |
|
|
|
| 154 |
| 170 |
| 46 |
| 170 |
| 147 |
| 170 |
| EG001 | Cohort A: Pembrolizumab Second Course | Qualified Cohort A participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 each 3-week cycle (Q3W) for up to 17 cycles (up to ~1 year). | 0 | 1 | 0 | 1 | 1 | 1 |
| EG002 | Cohort B: Pembrolizumab First Course | Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants were administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to ~2 years). | 63 | 84 | 19 | 84 | 79 | 84 |
| EG003 | Cohort B: Pembrolizumab Second Course | Qualified Cohort B participants who completed the first course of up to 35 administrations of pembrolizumab (~2 years) but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 17 cycles (up to ~1 year). | 0 | 4 | 2 | 4 | 4 | 4 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
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| Cardiac tamponade | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Myocarditis | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Pericardial effusion | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Pericarditis | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Gastroenteritis eosinophilic | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Subileus | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| General physical health deterioration | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Cholangitis | Hepatobiliary disorders | MedDRA 22.1 | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | MedDRA 22.1 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Infected skin ulcer | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Staphylococcal infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Superinfection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Postoperative ileus | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Liver function test abnormal | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
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| Colorectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
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| Infected neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
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| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
|
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Intracranial pressure increased | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Loss of consciousness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Device failure | Product Issues | MedDRA 22.1 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pulmonary thrombosis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyperthyroidism | Endocrine disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA 22.1 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 22.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Lymphoedema | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
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| Bronchial wall thickening | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
| D017437 |
| Skin and Connective Tissue Diseases |