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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3475-002 | Other Identifier | Merck | |
| 2012-003030-17 | EudraCT Number | ||
| KEYNOTE-002 | Other Identifier | Merck | |
| P08719 | Other Identifier | Schering Plough |
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This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL) who had progressed after prior therapy.
Initial Treatment Period:
Participants were initially randomized to receive either low-dose (2 mg/kg) pembrolizumab, higher dose (10 mg/kg) pembrolizumab or Investigator-choice chemotherapy (ICC). The four standard chemotherapy choices were: carboplatin + paclitaxel, paclitaxel alone, dacarbazine, or temozolomide. The randomization to either pembrolizumab or ICC was conducted in an open-label fashion.
The starting pembrolizumab dose was initially blinded to Investigators and participants until Amendment 03. With Amendment 03, all ongoing pembrolizumab participants were to be treated with open label, fixed dose pembrolizumab 200 mg, instead of a weight-based dosing of pembrolizumab.
Switch-to-Pembrolizumab Treatment Period:
Participants who were initially randomized to receive ICC and experienced progressive disease (PD) may have been eligible to switch to receiving pembrolizumab provided they met protocol-specified requirements for switching. Qualified participants were re-randomized to receive either pembrolizumab 2 mg/kg or pembrolizumab 10 mg/kg in a double-blind fashion. Participants who qualified to switch to pembrolizumab must have completed a washout period of ≥28 days from last dose of chemotherapy before receiving pembrolizumab. With Amendment 03, all switched-to-pembrolizumab participants were to be treated with open-label, fixed dose pembrolizumab 200 mg instead of a weight-based dosing of pembrolizumab.
Two interim and one final statistical analyses were planned for and conducted during this study:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pembrolizumab 2 mg/kg | Experimental | Participants were initially randomized to receive pembrolizumab 2 mg/kg intravenously (IV) once every 3 weeks (Q3W). With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
|
| Pembrolizumab 10 mg/kg | Experimental | Participants were initially randomized to receive pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
|
| Investigator-Choice Chemotherapy (ICC) | Active Comparator | Participants were initially randomized to receive 1 of 4 possible chemotherapy regimens decided at the treating institution (carboplatin+paclitaxel, paclitaxel alone, dacarbazine, or temozolomide). Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
|
| ICC→Pembrolizumab 2 mg/kg | Experimental | Participants who were initially randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Biological | IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) - Initial Treatment Period | 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 Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Analysis of PFS was based on an integrated radiology and oncology (IRO) assessment and was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median PFS based on the product limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for PFS. | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
| Interim Overall Survival (OS) - Initial Treatment Period | OS was defined as the time from randomization to death due to any cause. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS based on the product-limit (Kaplan-Meier) method for censored data is presented. This was the interim analysis for OS. | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
| Final Overall Survival (OS) - Initial Treatment Period | OS was defined as the time from randomization to death due to any cause. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS duration based on the product-limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for OS. | Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
| Measure | Description | Time Frame |
|---|---|---|
| Final Overall Survival (OS) By Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Status - Initial Treatment Period | OS was defined as the time from randomization to death due to any cause. Participants with an Allred Proportion Score (APS) ≥2 (membranous staining in ≥1% of cells for PD-L1) were considered to be PD-L1 Positive and participants with an APS of 0 or 1 were considered to be PD-L1 Negative. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS duration based on the product-limit (Kaplan-Meier) method for censored data by PD-L1 tumor expression status is presented. |
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Inclusion Criteria:
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 |
|---|---|---|---|
| 26115796 | Background | Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, Schachter J, Pavlick AC, Lewis KD, Cranmer LD, Blank CU, O'Day SJ, Ascierto PA, Salama AK, Margolin KA, Loquai C, Eigentler TK, Gangadhar TC, Carlino MS, Agarwala SS, Moschos SJ, Sosman JA, Goldinger SM, Shapira-Frommer R, Gonzalez R, Kirkwood JM, Wolchok JD, Eggermont A, Li XN, Zhou W, Zernhelt AM, Lis J, Ebbinghaus S, Kang SP, Daud A. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):908-18. doi: 10.1016/S1470-2045(15)00083-2. Epub 2015 Jun 23. | |
| 28961465 |
| Label | URL |
|---|---|
| Merck Oncology Clinical Trials Information | View source |
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This end of trial analysis is based on a trial closure database cutoff date of 31-Jan-2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pembrolizumab 2 mg/kg | Participants were initially randomized to receive pembrolizumab 2 mg/kg intravenously (IV) once every 3 weeks (Q3W). With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| FG001 | Pembrolizumab 10 mg/kg | Participants were initially randomized to receive pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| FG002 | Investigator-Choice Chemotherapy (ICC) | Participants were initially randomized to receive 1 of 4 possible chemotherapy regimens decided at the treating institution (carboplatin+paclitaxel, paclitaxel alone, dacarbazine, or temozolomide). Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| FG003 | ICC→Pembrolizumab 2 mg/kg | Participants who were initially randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) |
| FG004 | ICC→Pembrolizumab 10 mg/kg | Participants who were initially randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Initial Treatment Period |
|
| |||||||||||||||||||||
| Switch to Pembrolizumab Treatment Period |
|
The baseline analysis population consisted of all randomized participants. Participants were included in the group to which they were initially randomized for Baseline Characteristics.
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| ID | Title | Description |
|---|---|---|
| BG000 | Pembrolizumab 2 mg/kg | Participants were initially randomized to receive pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| 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 | Progression-free Survival (PFS) - Initial Treatment Period | 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 Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Analysis of PFS was based on an integrated radiology and oncology (IRO) assessment and was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median PFS based on the product limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for PFS. | The analysis population consisted of all randomized participants. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019)
Safety Population: All participants who received ≥1 dose of study drug. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (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 | Investigator-Choice Chemotherapy (ICC) Only | Participants received 1 of 4 possible chemotherapy regimens decided at the treating institution (carboplatin+paclitaxel, paclitaxel alone, dacarbazine, or temozolomide). This treatment group included the participants who remained on ICC through the final analysis. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal insufficiency | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | 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 |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| D003606 | Dacarbazine |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
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|
| ICC→Pembrolizumab 10 mg/kg | Experimental | Participants who were initially randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) |
|
|
| Carboplatin | Drug | Carboplatin per institutional standard |
|
|
| Paclitaxel | Drug | Paclitaxel per institutional standard |
|
|
| Dacarbazine | Drug | Dacarbazine per institutional standard |
|
|
| Temozolomide | Drug | Temozolomide per institutional standard |
|
|
| Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
| Overall Response Rate (ORR) - Initial Treatment Period | ORR was defined as the percentage of participants who had a 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) as assessed using RECIST 1.1. Analysis of ORR was not planned or conducted for the switch-to-pembrolizumab treatment groups. The percentage of participants who experienced a CR or PR is presented. This was the final analysis for ORR. | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
| Best Overall Response (BOR) - Initial Treatment Period | BOR was assessed by independent radiology review using RECIST 1.1 and was recorded from randomization until the last imaging assessment in this period. Response categories included: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. BOR for the Initial Treatment Period was based on IRO. BOR for participants during the Initial Treatment Period is presented. | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
| Best Overall Response (BOR) - Switch-to-Pembrolizumab Treatment Period | The BOR was assessed using RECIST 1.1 and was recorded from the start of the second line of study drug (pembrolizumab) until the last imaging assessment in this period. Response categories included: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For the switch-to-pembrolizumab treatment groups, BOR was based on independent review committee (IRC) assessment. The BOR for switched-to pembrolizumab treatment groups is presented. | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
| Duration of Response (DOR) - Initial Treatment Period | For participants who demonstrated a confirmed response (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, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. DOR analysis was based on IRO assessment. Analysis of DOR was not planned or analyzed for the switch-to-pembrolizumab treatment groups. Median DOR for participants who demonstrated a confirmed response is presented. | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
| Number of Participants Who Experienced an Adverse Event (AE) - Overall Study | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study drug, was also an AE. Participants were included in the treatment group in which an AE was experienced. The number of participants who experienced at least one AE is presented. | Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) - Overall Study | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of study drug, was also an AE. The number of participants who discontinued study drug due to an AE is presented. | Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
| Result |
| Hamid O, Puzanov I, Dummer R, Schachter J, Daud A, Schadendorf D, Blank C, Cranmer LD, Robert C, Pavlick AC, Gonzalez R, Hodi FS, Ascierto PA, Salama AKS, Margolin KA, Gangadhar TC, Wei Z, Ebbinghaus S, Ibrahim N, Ribas A. Final analysis of a randomised trial comparing pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory advanced melanoma. Eur J Cancer. 2017 Nov;86:37-45. doi: 10.1016/j.ejca.2017.07.022. |
| 35101941 | 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. |
| 33360855 | Derived | Robert C, Hwu WJ, Hamid O, Ribas A, Weber JS, Daud AI, Hodi FS, Wolchok JD, Mitchell TC, Hersey P, Dronca R, Joseph RW, Boutros C, Min L, Long GV, Schachter J, Puzanov I, Dummer R, Lin J, Ibrahim N, Diede SJ, Carlino MS, Joshua AM. Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma. Eur J Cancer. 2021 Feb;144:182-191. doi: 10.1016/j.ejca.2020.11.010. Epub 2020 Dec 24. |
| 32305010 | Derived | Lala M, Li TR, de Alwis DP, Sinha V, Mayawala K, Yamamoto N, Siu LL, Chartash E, Aboshady H, Jain L. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020 May;131:68-75. doi: 10.1016/j.ejca.2020.02.016. Epub 2020 Apr 15. |
| 31395089 | Derived | van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4. |
| 30736858 | Derived | Wang M, Chen C, Jemielita T, Anderson J, Li XN, Hu C, Kang SP, Ibrahim N, Ebbinghaus S. Are tumor size changes predictive of survival for checkpoint blockade based immunotherapy in metastatic melanoma? J Immunother Cancer. 2019 Feb 8;7(1):39. doi: 10.1186/s40425-019-0513-4. |
| 30202085 | Derived | Hamid O, Robert C, Ribas A, Hodi FS, Walpole E, Daud A, Arance AS, Brown E, Hoeller C, Mortier L, Schachter J, Long J, Ebbinghaus S, Ibrahim N, Butler M. Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006. Br J Cancer. 2018 Sep;119(6):670-674. doi: 10.1038/s41416-018-0207-6. Epub 2018 Sep 11. |
| 27596353 | Derived | Schadendorf D, Dummer R, Hauschild A, Robert C, Hamid O, Daud A, van den Eertwegh A, Cranmer L, O'Day S, Puzanov I, Schachter J, Blank C, Salama A, Loquai C, Mehnert JM, Hille D, Ebbinghaus S, Kang SP, Zhou W, Ribas A. Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma. Eur J Cancer. 2016 Nov;67:46-54. doi: 10.1016/j.ejca.2016.07.018. Epub 2016 Sep 2. |
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Switched to Pembrolizumab |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG001 | Pembrolizumab 10 mg/kg | Participants were initially randomized to receive pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| BG002 | Investigator-Choice Chemotherapy (ICC) | Participants were initially randomized to receive 1 of 4 possible chemotherapy regimens decided at the treating institution (carboplatin+paclitaxel, paclitaxel alone, dacarbazine, or temozolomide). Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Status | Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed by immunohistochemistry assay and scored on a unique melanoma (Allred Proportion Score [APS]/Melanoma [MEL]) scale of 0 to 5 points. Participants with an APS score of ≥2 (membranous staining in ≥1% of cells) were considered to be PD-L1 Positive and participants with an APS score of 0 or 1 were considered to be PD-L1 Negative. | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Pembrolizumab 2 mg/kg | Participants were initially randomized to receive pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| OG001 | Pembrolizumab 10 mg/kg | Participants were initially randomized to receive pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
| OG002 | Investigator-Choice Chemotherapy (ICC) | Participants were initially randomized to receive 1 of 4 possible chemotherapy regimens decided at the treating institution (carboplatin+paclitaxel, paclitaxel alone, dacarbazine, or temozolomide). Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) |
|
|
|
| Primary | Interim Overall Survival (OS) - Initial Treatment Period | OS was defined as the time from randomization to death due to any cause. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS based on the product-limit (Kaplan-Meier) method for censored data is presented. This was the interim analysis for OS. | The analysis population consisted of all randomized participants. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
|
|
|
|
| Primary | Final Overall Survival (OS) - Initial Treatment Period | OS was defined as the time from randomization to death due to any cause. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS duration based on the product-limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for OS. | The analysis population consisted of all randomized participants. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
|
|
|
|
| Secondary | Final Overall Survival (OS) By Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Status - Initial Treatment Period | OS was defined as the time from randomization to death due to any cause. Participants with an Allred Proportion Score (APS) ≥2 (membranous staining in ≥1% of cells for PD-L1) were considered to be PD-L1 Positive and participants with an APS of 0 or 1 were considered to be PD-L1 Negative. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS duration based on the product-limit (Kaplan-Meier) method for censored data by PD-L1 tumor expression status is presented. | The analysis population consisted of all randomized participants who had a PD-L1 tumor expression status assessment. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
|
|
|
|
| Secondary | Overall Response Rate (ORR) - Initial Treatment Period | ORR was defined as the percentage of participants who had a 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) as assessed using RECIST 1.1. Analysis of ORR was not planned or conducted for the switch-to-pembrolizumab treatment groups. The percentage of participants who experienced a CR or PR is presented. This was the final analysis for ORR. | The analysis population consisted of all randomized participants. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
|
|
|
| Secondary | Best Overall Response (BOR) - Initial Treatment Period | BOR was assessed by independent radiology review using RECIST 1.1 and was recorded from randomization until the last imaging assessment in this period. Response categories included: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. BOR for the Initial Treatment Period was based on IRO. BOR for participants during the Initial Treatment Period is presented. | The analysis population consisted of all randomized participants. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis. | Posted | Number | Percentage of Participants | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
|
|
|
| Secondary | Best Overall Response (BOR) - Switch-to-Pembrolizumab Treatment Period | The BOR was assessed using RECIST 1.1 and was recorded from the start of the second line of study drug (pembrolizumab) until the last imaging assessment in this period. Response categories included: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For the switch-to-pembrolizumab treatment groups, BOR was based on independent review committee (IRC) assessment. The BOR for switched-to pembrolizumab treatment groups is presented. | The analysis population consisted of all randomized participants in ICC who switched to receiving pembrolizumab. Participants were included in the treatment group to which they were re-randomized (switched) for this efficacy analysis. | Posted | Number | Percentage of Participants | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
|
|
|
| Secondary | Duration of Response (DOR) - Initial Treatment Period | For participants who demonstrated a confirmed response (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, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. DOR analysis was based on IRO assessment. Analysis of DOR was not planned or analyzed for the switch-to-pembrolizumab treatment groups. Median DOR for participants who demonstrated a confirmed response is presented. | The analysis population consisted of all randomized participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis. | Posted | Median | Full Range | Months | Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015) |
|
|
|
| Secondary | Number of Participants Who Experienced an Adverse Event (AE) - Overall Study | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study drug, was also an AE. Participants were included in the treatment group in which an AE was experienced. The number of participants who experienced at least one AE is presented. | The analysis population consisted of all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
|
|
|
| Secondary | Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) - Overall Study | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of study drug, was also an AE. The number of participants who discontinued study drug due to an AE is presented. | The analysis population consisted of all participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019) |
|
|
|
| 71 |
| 73 |
| 33 |
| 73 |
| 66 |
| 73 |
| EG001 | ICC→Pembrolizumab 2 mg/kg (Before Switch to Pembrolizumab) | Participants who were initially randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) | 0 | 53 | 15 | 53 | 52 | 53 |
| EG002 | ICC→Pembrolizumab 10 mg/kg (Before Switch to Pembrolizumab) | Participants who were initially randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) | 0 | 45 | 9 | 45 | 44 | 45 |
| EG003 | Pembrolizumab 2 mg/kg | Participants were initially randomized to receive pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) | 139 | 178 | 91 | 178 | 158 | 178 |
| EG004 | Pembrolizumab 10 mg/kg | Participants were initially randomized to receive pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to ~66 months) | 129 | 179 | 78 | 179 | 176 | 179 |
| EG005 | ICC→Pembrolizumab 2 mg/kg (After Switch to Pembrolizumab) | Participants who were initially randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) | 35 | 53 | 18 | 53 | 48 | 53 |
| EG006 | ICC→Pembrolizumab 10 mg/kg (After Switch to Pembrolizumab) | Participants who were initiall randomized to ICC, subsequently experienced confirmed progressive disease (PD) and met all switching criteria at study treatment Week 12, had the opportunity to switch to receive pembrolizumab 2 mg/kg or 10 mg/kg. Participants received pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to PD, toxicity, or choice. (Up to ~66 months) | 37 | 45 | 18 | 45 | 36 | 45 |
| Colitis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Intracranial tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Atrioventricular block complete | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cardiac ventricular disorder | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cardiogenic shock | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vertigo positional | Ear and labyrinth disorders | MedDRA 21.1 | Systematic Assessment |
|
| Addison's disease | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Adrenocortical insufficiency acute | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hyperparathyroidism | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypophysitis | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypopituitarism | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Secondary adrenocortical insufficiency | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Eye movement disorder | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Iritis | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Autoimmune colitis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Diverticular perforation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Diverticulum | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Gastric disorder | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Intussusception | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Large intestinal ulcer | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Large intestine perforation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Malabsorption | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Small intestinal perforation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cyst | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Infusion site extravasation | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Autoimmune hepatitis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hepatic necrosis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Anaphylactic reaction | Immune system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Appendicitis perforated | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Cellulitis streptococcal | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Infected cyst | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Infectious pleural effusion | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Mastitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Osteomyelitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Pelvic abscess | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Respiratory syncytial virus infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Salmonellosis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Soft tissue infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Streptococcal sepsis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Viral rash | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Fracture displacement | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Radiation necrosis | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Traumatic intracranial haemorrhage | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Diabetic metabolic decompensation | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Osteolysis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Spondylolisthesis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Colon cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Intestinal metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Invasive ductal breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Metastases to lymph nodes | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Metastases to meninges | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Oncologic complication | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Small cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hemiplegia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Lumbar radiculopathy | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Meningitis noninfective | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Myasthenic syndrome | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Myoclonus | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Partial seizures | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Spinal cord compression | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Transient ischaemic attack | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Device dislocation | Product Issues | MedDRA 21.1 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Postrenal failure | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pulmonary thrombosis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Lichenoid keratosis | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Circulatory collapse | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Poor venous access | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Venous thrombosis | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Abdominal abscess | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Postoperative wound infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cervical spine stenosis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Alveolitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA 21.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 21.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 21.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D003516 |
| Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.0106 | One-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.74 | 2-Sided | 95 | 0.57 | 0.96 | Numerator=Pembrolizumab 10 mg/kg Denominator=ICC | Superiority or Other (legacy) |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.2905 | Two-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.87 | 2-Sided | 95 | 0.67 | 1.12 | Numerator=Pembrolizumab 10 mg/kg Denominator=Pembrolizumab 2 mg/kg | Superiority or Other (legacy) |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.0023 | One-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.71 | 2-Sided | 95 | 0.55 | 0.90 | Numerator=Pembrolizumab 10 mg/kg Denominator=ICC | Superiority or Other (legacy) |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.1490 | Two-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.84 | 2-Sided | 95 | 0.66 | 1.07 | Numerator=Pembrolizumab 10 mg/kg Denominator=Pembrolizumab 2 mg/kg | Superiority or Other (legacy) |
| PD-L1 Negative |
|
|
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.0208 | One-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.70 | 2-Sided | 95 | 0.50 | 0.99 | Numerator=Pembrolizumab 10 mg/kg Denominator=ICC | Superiority or Other (legacy) | PD-L1 Positive Participants |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.0496 | Two-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.71 | 2-Sided | 95 | 0.50 | 1.00 | Numerator=Pembrolizumab 10 mg/kg Denominator=Pembrolizumab 2 mg/kg | Superiority or Other (legacy) | PD-L1 Positive Participants |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.6043 | One-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 1.07 | 2-Sided | 95 | 0.65 | 1.76 | Numerator=Pembrolizumab 2 mg/kg Denominator=ICC | Superiority or Other (legacy) | PD-L1 Negative Participants |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.0335 | One-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.62 | 2-Sided | 95 | 0.37 | 1.04 | Numerator=Pembrolizumab 10 mg/kg Denominator=ICC | Superiority or Other (legacy) | PD-L1 Negative Participants |
| Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels [≥110% ULN]); & BRAF mutational status (mutant vs. wild-type) | Log Rank | 0.1504 | Two-sided p-value based on stratified log rank test | Hazard Ratio (HR) | 0.71 | 2-Sided | 95 | 0.44 | 1.13 | Numerator=Pembrolizumab 10 mg/kg Denominator=Pembrolizumab 2 mg/kg | Superiority or Other (legacy) | PD-L1 Negative Participants |
|
| Stable Disease |
|
| Progressive Disease |
|
| Not Evaluable |
|
| No Disease |
|
| No Assessment |
|
| Stable Disease |
|
| Progressive Disease |
|
| Not Evaluable |
|
| No Assessment |
|