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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3475-032 | Other Identifier | Merck Protocol Number | |
| KEYNOTE-032 | Other Identifier | Merck |
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The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and efficacy of three doses of pembrolizumab (MK-3475) in adult Chinese participants with locally advanced or metastatic non-small-cell lung cancer (NSCLC).
Cycle 1 is 28 days long; subsequent cycles are 21 days long.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pembrolizumab 2 mg/kg | Experimental | Participants will receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
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| Pembrolizumab 10 mg/kg | Experimental | Participants will receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
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| Pembrolizumab 200 mg Fixed Dose | Experimental | Participants will receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Biological | IV infusion |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced at least one AE was reported per protocol for the first course of treatment. | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| Number of Participants Who Discontinued Study Drug Due to an AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who discontinued study treatment due to an AE was reported per protocol for the first course of treatment. | Up to ~12 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| Single Dose PK: Area Under the Plasma Concentration Curve From 0-28 Days (AUC[0-28 Days]) of Pembrolizumab | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate AUC(0-28 days) following single dose administration for the first course of treatment. | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Central Radiologists' Review | ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions) as assessed by central radiologists' review per RECIST 1.1 which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR per RECIST 1.1 as assessed by central radiologists' review was reported for each arm per protocol for the first course of treatment. |
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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 |
|---|---|---|---|
| 32134163 | Result | Ma Y, Fang W, Zhang Y, Yang Y, Hong S, Zhao Y, Xie S, Ge J, Zhou H, Zhao H, Zhang L. KEYNOTE-032: A Randomized Phase I Study of Pembrolizumab in Chinese Patients with Advanced Non-Small Cell Lung Cancer. Oncologist. 2020 Aug;25(8):650-e1145. doi: 10.1634/theoncologist.2020-0067. Epub 2020 Mar 5. |
| Label | URL |
|---|---|
| Merck Oncology Clinical Trials Information | View source |
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Of 44 participants randomized, 42 received treatment. Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures, respectively.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pembrolizumab 2 mg/kg | Participants received pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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 17, 2020 |
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| Single-Dose PK: Maximum Plasma Concentration (Cmax) of Pembrolizumab | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate Cmax following single dose administration for the first course of treatment. | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
| Single Dose PK: Time to Cmax (Tmax) of Pembrolizumab | Tmax was defined as the time required post dosing to reach a maximum plasma concentration of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate Tmax following single dose administration for the first course of treatment. | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
| Single Dose PK: Apparent Terminal Half-Life (t1/2) of Pembrolizumab | t½ was defined as the time required to divide the pembrolizumab plasma concentration by two after reaching pseudo-equilibrium, following a single dose of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate t½ following single dose administration for the first course of treatment. | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
| Multiple Dose PK: Trough Plasma Concentration (Ctrough) of Pembrolizumab | Ctrough was defined as the minimum concentration that occurred immediately prior to the administration of pembrolizumab in Cycle 8. Blood samples were collected pre-dose at Cycle 8 to estimate Ctrough following multiple dose administrations of pembrolizumab for the first course of treatment. | Cycle 8 Day 1: pre-dose [-1 to 0 hour]. (Cycle 1 = 28 days, Cycles 2-8 = 21 days). |
| Multiple Dose PK: AUC(0-21 Days) of Pembrolizumab at Steady State | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 to assess AUC(0-21 days) at steady state for the first course of treatment. | Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days). |
| Multiple Dose PK: Cmax of Pembrolizumab at Steady State | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 to assess Cmax assessment at steady state for the first course of treatment. | Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days). |
| Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| ORR Per Immune-related RECIST (irRECIST) as Assessed by Central Radiologists' Review | ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-related Complete Response (irCR: Disappearance of all target lesions and non-target) or an immune-related Partial Response (irPR: At least a 30% decrease in the sum of diameters of target lesions, stability of non-target lesions no new lesions) after a single PD per irRECIST as assessed by central radiologists' review. Per RECIST 1.1, CR or PR was confirmed by repeated radiographic assessment no less than 4 weeks from the first documented response. If site-assessed PD was verified by the central imaging vendor, the site could elect to continue treatment, repeat imaging ≥4 weeks later and assess tumor response or confirmed progression per irRECIST. The percentage of participants who experienced a CR or PR per RECIST 1.1 or irCR or irPR per irRECIST as assessed by central radiologists' review was reported for each arm per protocol for first course of treatment. | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by Central Radiologists' Review | For participants who demonstrated a confirmed CR (disappearance of all lesions) or confirmed PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by central radiologists' review, DOR was defined as the time from first documented evidence of a CR or PR until disease progression or death. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR per RECIST 1.1 as assessed by central radiologists' review for all participants who experienced a confirmed CR or PR was reported for each arm per protocol for the first course of treatment. | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| DOR Per irRECIST as Assessed by Central Radiologists' Review | For participants who demonstrated confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or CR or PR after a single PD, DOR was defined as the time from the first documented CR or PR, or irCR or irPR, until an immune-related progressive disease (irPD) 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. Per irRECIST, irPD was defined as after a single PD, ≥20% increase in the sum of diameters of target lesions, or unequivocal worsening of non-target lesions or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. DOR per irRECIST assessed by central radiologists' review for all participants with confirmed CR or PR or irCR or irPR was reported for each arm per protocol for the first course of treatment. | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Central Radiologists' Review | PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as either a 20% increase from nadir in target lesions, unequivocal progression of nontarget lesions, or the appearance of new lesions. PFS per RECIST 1.1 as assessed by central radiologists' review was reported for each arm per protocol for the first course of treatment. | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| PFS Per irRECIST as Assessed by Central Radiologists' Review | PFS was defined as the time from randomization to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurred first. Per iRECIST, iCPD is defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. PFS per irRECIST as assessed by central radiologists' review is reported for each arm per protocol for the first course of treatment. | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was reported for each arm using a 19-Sept-2017 data cut-off date per protocol for the first course of treatment. | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
| FG001 | Pembrolizumab 10 mg/kg | Participants received pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
| FG002 | Pembrolizumab 200 mg Fixed Dose | Participants received pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
| Received First Course of Pembrolizumab |
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| Received Second Course of Pembrolizumab |
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| COMPLETED |
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| NOT COMPLETED |
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All randomized participants that received at least one dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Pembrolizumab 2 mg/kg | Participants received pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
| BG001 | Pembrolizumab 10 mg/kg | Participants received pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
| BG002 | Pembrolizumab 200 mg Fixed Dose | Participants received pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 | ||||||||||||||||||||||||||
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| Primary | Number of Participants Who Experienced an Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced at least one AE was reported per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Primary | Number of Participants Who Discontinued Study Drug Due to an AE | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who discontinued study treatment due to an AE was reported per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment. | Posted | Count of Participants | Participants | Up to ~12 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Primary | Single Dose PK: Area Under the Plasma Concentration Curve From 0-28 Days (AUC[0-28 Days]) of Pembrolizumab | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate AUC(0-28 days) following single dose administration for the first course of treatment. | All randomized participants who received a pembrolizumab dose, with available pharmacokinetic (PK) data, and who did not have any protocol deviation interfering with PK. | Posted | Geometric Mean | 95% Confidence Interval | μg•day/mL | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
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| Primary | Single-Dose PK: Maximum Plasma Concentration (Cmax) of Pembrolizumab | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate Cmax following single dose administration for the first course of treatment. | All randomized participants who received a pembrolizumab dose, with available PK data, and who did not have any protocol deviation interfering with PK. | Posted | Geometric Mean | 95% Confidence Interval | μg/mL | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
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| Primary | Single Dose PK: Time to Cmax (Tmax) of Pembrolizumab | Tmax was defined as the time required post dosing to reach a maximum plasma concentration of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate Tmax following single dose administration for the first course of treatment. | All randomized participants who received a pembrolizumab dose, with available PK data, and who did not have any protocol deviation interfering with PK. | Posted | Median | Full Range | day | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
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| Primary | Single Dose PK: Apparent Terminal Half-Life (t1/2) of Pembrolizumab | t½ was defined as the time required to divide the pembrolizumab plasma concentration by two after reaching pseudo-equilibrium, following a single dose of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate t½ following single dose administration for the first course of treatment. | All randomized participants who received a pembrolizumab dose, with available PK data, and who did not have any protocol deviation interfering with PK. | Posted | Median | Full Range | Day | Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days |
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| Primary | Multiple Dose PK: Trough Plasma Concentration (Ctrough) of Pembrolizumab | Ctrough was defined as the minimum concentration that occurred immediately prior to the administration of pembrolizumab in Cycle 8. Blood samples were collected pre-dose at Cycle 8 to estimate Ctrough following multiple dose administrations of pembrolizumab for the first course of treatment. | All randomized participants who received a pembrolizumab dose, had available Ctrough data, and who did not have any protocol deviation interfering with PK. | Posted | Geometric Mean | 95% Confidence Interval | μg/mL | Cycle 8 Day 1: pre-dose [-1 to 0 hour]. (Cycle 1 = 28 days, Cycles 2-8 = 21 days). |
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| Primary | Multiple Dose PK: AUC(0-21 Days) of Pembrolizumab at Steady State | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 to assess AUC(0-21 days) at steady state for the first course of treatment. | All randomized participants who received a pembrolizumab dose, had available AUC(0-21 days) data, and who did not have any protocol deviation interfering with PK. | Posted | Geometric Mean | 95% Confidence Interval | μg•day/mL | Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days). |
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| Primary | Multiple Dose PK: Cmax of Pembrolizumab at Steady State | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 to assess Cmax assessment at steady state for the first course of treatment. | All randomized participants who received a pembrolizumab dose, had available Cmax data, and who did not have any protocol deviation interfering with PK. | Posted | Geometric Mean | 95% Confidence Interval | g/mL | Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days). |
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| Secondary | Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Central Radiologists' Review | ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions) as assessed by central radiologists' review per RECIST 1.1 which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR per RECIST 1.1 as assessed by central radiologists' review was reported for each arm per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment and with measurable disease at baseline as assessed by central radiology review. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Secondary | ORR Per Immune-related RECIST (irRECIST) as Assessed by Central Radiologists' Review | ORR was defined as the percentage of participants who had confirmed responses assessed using RECIST 1.1 before PD or an immune-related Complete Response (irCR: Disappearance of all target lesions and non-target) or an immune-related Partial Response (irPR: At least a 30% decrease in the sum of diameters of target lesions, stability of non-target lesions no new lesions) after a single PD per irRECIST as assessed by central radiologists' review. Per RECIST 1.1, CR or PR was confirmed by repeated radiographic assessment no less than 4 weeks from the first documented response. If site-assessed PD was verified by the central imaging vendor, the site could elect to continue treatment, repeat imaging ≥4 weeks later and assess tumor response or confirmed progression per irRECIST. The percentage of participants who experienced a CR or PR per RECIST 1.1 or irCR or irPR per irRECIST as assessed by central radiologists' review was reported for each arm per protocol for first course of treatment. | All randomized participants that received at least one dose of study treatment and with measurable disease at baseline as assessed by central radiology review. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Secondary | Duration of Response (DOR) Per RECIST 1.1 as Assessed by Central Radiologists' Review | For participants who demonstrated a confirmed CR (disappearance of all lesions) or confirmed PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by central radiologists' review, DOR was defined as the time from first documented evidence of a CR or PR until disease progression or death. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR per RECIST 1.1 as assessed by central radiologists' review for all participants who experienced a confirmed CR or PR was reported for each arm per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment, had measurable disease at baseline as assessed by central radiology review, and who demonstrated a confirmed response (CR or PR). No participants in the Pembrolizumab 2 mg/kg group were eligible for this analysis. | Posted | Median | Full Range | Months | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Secondary | DOR Per irRECIST as Assessed by Central Radiologists' Review | For participants who demonstrated confirmed CR (disappearance of all target lesions and non-target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 or CR or PR after a single PD, DOR was defined as the time from the first documented CR or PR, or irCR or irPR, until an immune-related progressive disease (irPD) 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. Per irRECIST, irPD was defined as after a single PD, ≥20% increase in the sum of diameters of target lesions, or unequivocal worsening of non-target lesions or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. DOR per irRECIST assessed by central radiologists' review for all participants with confirmed CR or PR or irCR or irPR was reported for each arm per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment, had measurable disease at baseline as assessed by central radiology review, and who demonstrated a confirmed response (iCR or iPR). No participants in the Pembrolizumab 2 mg/kg group were eligible for this analysis. | Posted | Median | Full Range | Months | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Secondary | Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Central Radiologists' Review | PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as either a 20% increase from nadir in target lesions, unequivocal progression of nontarget lesions, or the appearance of new lesions. PFS per RECIST 1.1 as assessed by central radiologists' review was reported for each arm per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | Months | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Secondary | PFS Per irRECIST as Assessed by Central Radiologists' Review | PFS was defined as the time from randomization to the first documented immune-based confirmed progressive disease (iCPD) or death due to any cause, whichever occurred first. Per iRECIST, iCPD is defined as worsening of any existing cause of progression, or the appearance of any other cause of progression, relative to the initial appearance of progressive disease by RECIST 1.1. PFS per irRECIST as assessed by central radiologists' review is reported for each arm per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | Months | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
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| Secondary | Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was reported for each arm using a 19-Sept-2017 data cut-off date per protocol for the first course of treatment. | All randomized participants that received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | Months | Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017) |
|
Up to ~65 months (through End of Trial database cut-off date of 31-Dec-2021)
All-Cause Mortality was reported according to treatment course for all randomized participants.
Serious and Other AEs were reported according to treatment course for all randomized participants who received ≥1 dose of study treatment. Per protocol, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pembrolizumab 2 mg/kg First Course | Participants received pembrolizumab 2 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days | 11 | 14 | 2 | 14 | 14 | 14 |
| EG001 | Pembrolizumab 10 mg/kg First Course | Participants received pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. | 12 | 15 | 1 | 13 | 13 | 13 |
| EG002 | Pembrolizumab 200 mg Fixed Dose First Course | Participants received pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 was 28 days and subsequent cycles were 21 days. | 13 | 15 | 3 | 15 | 14 | 15 |
| EG003 | Pembrolizumab 2 mg/kg Second Course | Eligible participants who stopped the initial course of pembrolizumab (2 mg/kg administered IV Q3W for up to 35 administrations) with Stable Disease (SD) or better but progressed after discontinuation initiated a second course of pembrolizumab at the same dose per the investigator's discretion for up to 17 cycles (up to approximately 1 additional year). | 1 | 1 | 0 | 1 | 0 | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eyelid ptosis | Eye disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Lymph node pain | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Faeces hard | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Swelling face | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Heart rate increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Neutrophil count increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Skin swelling | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 24.1 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Sep 27, 2022 |
| Prot_SAP_001.pdf |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| OG002 | Pembrolizumab 200 mg Fixed Dose | Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
|
|
|
|
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
|
|
|
|
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
| OG002 | Pembrolizumab 200 mg Fixed Dose | Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
| OG001 |
| Pembrolizumab 10 mg/kg |
Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
| OG002 | Pembrolizumab 200 mg Fixed Dose | Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
| OG002 | Pembrolizumab 200 mg Fixed Dose | Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
| OG001 | Pembrolizumab 10 mg/kg | Participants receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
| OG002 | Pembrolizumab 200 mg Fixed Dose | Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. |
|
|
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
|
|
Participants receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days.
|
|
|
|