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| ID | Type | Description | Link |
|---|---|---|---|
| 163421 | Registry Identifier | JAPIC-CTI | |
| MK-3475-189 | Other Identifier | Merck | |
| KEYNOTE-189 | Other Identifier | Merck |
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This is a Japan Extension Study of Global Study MK-3475-189 (NCT02578680). This is an efficacy and safety study of pembrolizumab (MK-3475) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone in adult Japanese participants with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned to receive pembrolizumab combined with pemetrexed/platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed/platinum (Investigators choice of cisplatin or carboplatin).
With Amendment 11 (effective date 31-Jan-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.
The primary hypothesis is that pembrolizumab in combination with pemetrexed/platinum chemotherapy prolongs Progression-Free Survival (PFS) and Overall Survival (OS) compared to pemetrexed/platinum chemotherapy alone.
The MK-3475-189-Japan Extension Study will be identical to the global study (e.g. inclusion and exclusion criteria, study primary and secondary outcome measures and study procedures).
The MK-3475-189-Japanese Extension Study enrolled a total of 30 participants and the analyses included 10 participants (pembrolizumab =4; control = 6) that had been previously enrolled in the MK-3475-189 global study (NCT02578680), resulting in a total of 40 participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pembrolizumab with Pemetrexed and Platinum Chemotherapy Followed by Pembrolizumab and Pemetrexed | Experimental | Participants receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who receive pembrolizumab 200 mg IV Q3W for up to 2 years, but experience disease progression, are eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
|
| Placebo with Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed | Active Comparator | Participants receive saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who receive saline placebo, but experience disease progression, can switch over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who switch over to pembrolizumab 200 mg IV Q3W, but experience disease progression, are eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab 200 mg | Biological | IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging | 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 ≥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 also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented. | Up to approximately 31 months |
| 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 analysis were censored at the date of the last follow-up. The OS is presented. | Up to approximately 31 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) as Assessed by Investigator Immune-related RECIST (irRECIST) Response Criteria | PFS was defined as the time from randomization to the first documented immune-related progressive disease (irPD) or death due to any cause, whichever occurred first. Per irRECIST, irPD was confirmed if any of the following are observed in 2 scans performed at least 4 weeks apart: target lesion sum of diameters remains ≥20 % and at least 5 mm absolute increase compared to nadir; non-target disease resulting in initial PD is qualitatively worse; new lesion resulting in initial irPD is qualitatively worse; additional new lesion(s) since last evaluation; or additional new non-target lesion progression since last evaluation. The PFS per irRECIST 1.1 is presented. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Hospital Organization Nagoya Medical Center ( Site 0324) | Nagoya | Aichi-ken | 460-0001 | Japan | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34036692 | Result | Horinouchi H, Nogami N, Saka H, Nishio M, Tokito T, Takahashi T, Kasahara K, Hattori Y, Ichihara E, Adachi N, Noguchi K, Souza F, Kurata T. Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non-small-cell lung cancer: KEYNOTE-189 Japan Study. Cancer Sci. 2021 Aug;112(8):3255-3265. doi: 10.1111/cas.14980. Epub 2021 Jun 15. | |
| 38642841 |
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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Four participants randomized to placebo treatment had switched over to receive pembrolizumab monotherapy. Participants receiving pembrolizumab in the first course and those who switched over from placebo to pembrolizumab were eligible to receive a second course of pembrolizumab if they met certain criteria. Data from the second course treatment contributed to safety data only. Final analyses for all primary and secondary outcome measures were done at the protocol-specified cutoff (20-May-2019).
The Japanese Extension study for MK-3475-189 enrolled a total of 30 participants and the analyses included 10 participants (pembrolizumab =4; control = 6) that had been previously enrolled in the global study for MK-3475-189 (NCT02578680), resulting in a total of 40 participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pembrolizumab With Pemetrexed and Platinum Chemotherapy Followed by Pembrolizumab and Pemetrexed | Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received pembrolizumab 200 mg IV Q3W for up to 2 years, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
| 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 | Yes | No | No | Study Protocol | Nov 6, 2017 | May 7, 2020 |
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| Cisplatin | Drug | IV infusion |
|
| Carboplatin | Drug | IV infusion |
|
| Pemetrexed | Drug | IV infusion |
|
| Folic acid 350-1000 μg | Dietary Supplement | Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed. |
|
| Vitamin B12 1000 μg | Dietary Supplement | Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration. |
|
| Dexamethasone 4 mg | Drug | For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration. |
|
| Saline solution | Drug | IV infusion |
|
| Up to approximately 31 months |
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging | For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. | Up to approximately 31 months |
| Number of Participants Who Experienced an Adverse Event (AE) | An adverse event was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product which did not necessarily have a causal relationship with this treatment. An adverse event was any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the study drug was also an adverse event. Per protocol, final analysis for this outcome measure was performed for the first course of pembrolizumab or placebo treatment. The number of participants who experienced an AE is reported. | Up to approximately 24 months |
| Number of Participants Who Discontinued Any Study Drug Due to an AE | An adverse event was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product which did not necessarily have a causal relationship with this treatment. An adverse event was any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the study drug was also an adverse event. Per protocol, final analysis for this outcome measure was performed for the first course of pembrolizumab or placebo treatment. The number of participants who discontinued study treatment due to an AE is presented. | Up to approximately 21 months |
| Up to approximately 31 months |
| Kurume University Hospital ( Site 0326) |
| Kurume |
| Fukuoka |
| 830-0011 |
| Japan |
| Hyogo Cancer Center ( Site 0325) | Akashi | Hyōgo | 673-8558 | Japan |
| Kanazawa University Hospital ( Site 0328) | Kanazawa | Ishikawa-ken | 920-8641 | Japan |
| Kansai Medical University Hospital ( Site 0313) | Hirakata | Osaka | 573-1191 | Japan |
| Shizuoka Cancer Center Hospital and Research Institute ( Site 0322) | Sunto-gun | Shizuoka | 411-8777 | Japan |
| National Hospital Organization Shikoku Cancer Center ( Site 0303) | Matsuyama | 791-0280 | Japan |
| Okayama University Hospital ( Site 0327) | Okayama | 700-8558 | Japan |
| National Cancer Center Hospital ( Site 0301) | Tokyo | 104-0045 | Japan |
| The Cancer Institute Hospital of JFCR ( Site 0323) | Tokyo | 135-8550 | Japan |
| Gadgeel SM, Rodriguez-Abreu D, Halmos B, Garassino MC, Kurata T, Cheng Y, Jensen E, Shamoun M, Rajagopalan K, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Metastatic NSCLC With Programmed Cell Death Ligand 1 Tumor Proportion Score Less Than 1%: Pooled Analysis of Outcomes After Five Years of Follow-Up. J Thorac Oncol. 2024 Aug;19(8):1228-1241. doi: 10.1016/j.jtho.2024.04.011. Epub 2024 Apr 18. |
| 37465924 | Derived | Cheng Y, Yang JC, Okamoto I, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Yan Y, Xiao S, Lin J, Pietanza MC, Kurata T. Pembrolizumab plus chemotherapy for advanced non-small-cell lung cancer without tumor PD-L1 expression in Asia. Immunotherapy. 2023 Sep;15(13):1029-1044. doi: 10.2217/imt-2023-0043. Epub 2023 Jul 19. |
| 35930972 | Derived | Rolfo C, Hess LM, Jen MH, Peterson P, Li X, Liu H, Lai Y, Sugihara T, Kiiskinen U, Vickers A, Summers Y. External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer. ESMO Open. 2022 Aug;7(4):100551. doi: 10.1016/j.esmoop.2022.100551. Epub 2022 Aug 2. |
| FG001 | Placebo With Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed | Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received saline placebo, but experienced disease progression, were switched over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who had switched over to pembrolizumab 200 mg IV Q3W, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
| Treated |
|
| Switched to Pembrolizumab Monotherapy |
|
| Second Course Treatment With Pembrolizumab Monotherapy |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The Baseline Analysis Population consisted of all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Pembrolizumab With Pemetrexed and Platinum Chemotherapy Followed by Pembrolizumab and Pemetrexed | Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received pembrolizumab 200 mg IV Q3W for up to 2 years, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
| BG001 | Placebo With Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed | Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received saline placebo, but experienced disease progression, were switched over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who had switched over to pembrolizumab 200 mg IV Q3W, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status | Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from an archival or newly obtained biopsy. Participants with a TPS ≥1% were classified as PD-L1 positive and participants with a TPS <1% were classified as PD-L1 negative. | Count of Participants | Participants |
| |||||||||||||||
| Platinum Chemotherapy | Participants were classified according to the type of platinum chemotherapy the Investigator chose for them to receive: Cisplatin or Carboplatin. | Count of Participants | Participants |
| |||||||||||||||
| Smoking Status | Participants were classified according to their smoking status: Never Smoker or Former/Current Smoker. | 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging | 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 ≥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 also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented. | The analysis population consisted of all randomized participants. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 31 months |
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| Primary | 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 analysis were censored at the date of the last follow-up. The OS is presented. | The analysis population consisted of all randomized participants. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 31 months |
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| Secondary | Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. | The analysis population consisted of all randomized participants. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to approximately 31 months |
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| Secondary | Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging | For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. | The analysis population consisted of all randomized participants who experienced a confirmed CR or confirmed PR. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 31 months |
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| Secondary | Number of Participants Who Experienced an Adverse Event (AE) | An adverse event was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product which did not necessarily have a causal relationship with this treatment. An adverse event was any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the study drug was also an adverse event. Per protocol, final analysis for this outcome measure was performed for the first course of pembrolizumab or placebo treatment. The number of participants who experienced an AE is reported. | The analysis population consisted of all randomized participants who received ≥1 dose of study drug. | Posted | Count of Participants | Participants | Up to approximately 24 months |
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| Secondary | Number of Participants Who Discontinued Any Study Drug Due to an AE | An adverse event was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product which did not necessarily have a causal relationship with this treatment. An adverse event was any unfavourable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the study drug was also an adverse event. Per protocol, final analysis for this outcome measure was performed for the first course of pembrolizumab or placebo treatment. The number of participants who discontinued study treatment due to an AE is presented. | The analysis population consisted of all randomized participants who received ≥1 dose of study drug. | Posted | Count of Participants | Participants | Up to approximately 21 months |
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| Other Pre-specified | Progression-Free Survival (PFS) as Assessed by Investigator Immune-related RECIST (irRECIST) Response Criteria | PFS was defined as the time from randomization to the first documented immune-related progressive disease (irPD) or death due to any cause, whichever occurred first. Per irRECIST, irPD was confirmed if any of the following are observed in 2 scans performed at least 4 weeks apart: target lesion sum of diameters remains ≥20 % and at least 5 mm absolute increase compared to nadir; non-target disease resulting in initial PD is qualitatively worse; new lesion resulting in initial irPD is qualitatively worse; additional new lesion(s) since last evaluation; or additional new non-target lesion progression since last evaluation. The PFS per irRECIST 1.1 is presented. | The analysis population consisted of all randomized participants. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 31 months |
|
Up to approximately 80 months
All participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an adverse event (AE) unless treatment related. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression (NP), malignant NP, and disease progression not related to treatment were excluded. All-cause mortality and AEs analyzed for both study arms, participants switched over from placebo to pembrolizumab, and those who received second course pembrolizumab if applicable.
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 With Pemetrexed and Platinum Chemotherapy Followed by Pembrolizumab and Pemetrexed | Participants received pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received pembrolizumab 200 mg IV Q3W for up to 2 years, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. | 15 | 25 | 9 | 25 | 25 | 25 |
| EG001 | Placebo With Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed | Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received saline placebo, but experienced disease progression, were switched over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who had switched over to pembrolizumab 200 mg IV Q3W, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. | 11 | 15 | 6 | 15 | 15 | 15 |
| EG002 | Placebo Switched Over to Pembrolizumab Monotherapy | Qualified participants who received saline placebo with pemetrexed and platinum chemotherapy followed by placebo and pemetrexed, and who experienced disease progression, were switched over to receive pembrolizumab monotherapy 200 mg IV on Day 1 Q3W for up to 2 years. | 4 | 4 | 1 | 4 | 4 | 4 |
| EG003 | Second Course Treatment for the Pembrolizumab With Pemetrexed and Platinum Chemotherapy Arm | Participants who received pembrolizumab with pemetrexed and platinum chemotherapy followed by pembrolizumab and pemetrexed during the initial treatment, and met certain criteria, initiated a second course of pembrolizumab monotherapy at 200 mg IV Q3W for up to 1 additional year. | 1 | 1 | 0 | 1 | 0 | 1 |
| EG004 | Second Course Treatment for the Placebo Switched Over to Pembrolizumab Monotherapy Arm | Participants who were switched from saline placebo to receive pembrolizumab monotherapy, and met certain criteria, initiated a second course of pembrolizumab monotherapy at 200 mg IV Q3W for up to 1 additional year. | 0 | 0 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal insufficiency | Endocrine disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Bacterial infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Oesophageal infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Parotitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Radiation oesophagitis | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Tumour necrosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Toxic epidermal necrolysis | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypoacusis | Ear and labyrinth disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Conjunctivitis allergic | Eye disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Bowel movement irregularity | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Large intestine polyp | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Oral hyperaesthesia | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Infusion site extravasation | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Puncture site pain | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Lymph gland infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Forearm fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Thyroid hormones decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Thyroxine free increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Tri-iodothyronine free decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Leukoencephalopathy | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 26.0 | 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 |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 16, 2017 | May 7, 2020 | 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 |
| D002945 | Cisplatin |
| D016190 | Carboplatin |
| D000068437 | Pemetrexed |
| D005492 | Folic Acid |
| D014805 | Vitamin B 12 |
| D003907 | Dexamethasone |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
| D011622 | Pterins |
| D011621 | Pteridines |
| D045728 | Corrinoids |
| D045725 | Tetrapyrroles |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D013259 | Steroids, Fluorinated |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| TPS ≥1% |
|
| Not Evaluable |
|
| Carboplatin |
|
| Former/Current Smoker |
|
|
|
|
|
|
| OG001 | Placebo With Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed | Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received saline placebo, but experienced disease progression, were switched over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who had switched over to pembrolizumab 200 mg IV Q3W, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
|
|
| OG001 | Placebo With Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed | Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received saline placebo, but experienced disease progression, were switched over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who had switched over to pembrolizumab 200 mg IV Q3W, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
|
|
| OG001 | Placebo With Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed | Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received saline placebo, but experienced disease progression, were switched over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who had switched over to pembrolizumab 200 mg IV Q3W, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
|
|
| OG001 |
| Placebo With Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed |
Participants received saline placebo IV PLUS pemetrexed 500 mg/m^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m^2 IV Q3W until progression. Participants who received saline placebo, but experienced disease progression, were switched over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who had switched over to pembrolizumab 200 mg IV Q3W, but experienced disease progression, were eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year. |
|
|