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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3475-224 | Other Identifier | MSD | |
| KEYNOTE-224 | Other Identifier | MSD | |
| 163434 | Other Identifier | JAPIC-CTI | |
| 2015-004566-28 | EudraCT Number |
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This is a efficacy and safety study of pembrolizumab (MK-3475, KEYTRUDA®) as monotherapy in participants with hepatocellular carcinoma (HCC) in two cohorts: participants with advanced HCC and with no curative option after disease progression on sorafenib or intolerance of sorafenib (Cohort 1) or who had not received treatment for systemic disease (Cohort 2). Study participants may receive pembrolizumab once every 3 weeks for up to 35 initial cycles (up to approximately 2 years) and a potential additional 17 cycles in a re-treatment phase (approximately an additional 1 year of treatment) .
The primary objective of this study is to determine the Objective Response Rate (ORR) of pembrolizumab given as monotherapy in participants with HCC.
Effective with Amendment 7: Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Hepatocellular Carcinoma (HCC)-Prior Systemic Therapy with Sorafenib | Experimental | Participants with previously systemically treated HCC received a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
|
| Cohort 2: HCC-Systemic Therapy Naïve | Experimental | Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Biological | Intravenous (IV) infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target and non-target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented. | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Response (DOR) | DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target and non-target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target and non-target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed, started a new anti-cancer therapy, been lost to follow-up, or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. The DOR per RECIST 1.1 for all participants who had a confirmed CR or PR is presented. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41453647 | Derived | Chan SL, Finn RS, Edeline J, Ogasawara S, Knox JJ, Daniele B, Ryoo BY, Merle P, Bouattour M, Lim HY, Chao Y, Yau T, Haber BA, Malhotra U, Siegel AB, Liu CC, Kudo M, Cheng AL. Effect of pembrolizumab on viral hepatitis load and transaminases in advanced hepatocellular carcinoma. Ann Hepatol. 2026 Jan-Jun;31(1):102169. doi: 10.1016/j.aohep.2025.102169. Epub 2025 Dec 24. | |
| 36852452 |
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
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Per protocol, final analyses of all outcome measures were planned to be performed during the first course of therapy and collection of adverse events and all-cause mortality were planned to be done in both first and second courses.
This study had 2 cohorts with each cohort starting treatment at a different time period during the study.
One participant allocated to Cohort 1 withdrew from the study before receiving treatment. This participant was not eligible for safety or efficacy analysis.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: Hepatocellular Carcinoma (HCC)-Prior Systemic Therapy With Sorafenib | Participants with previously systemically treated HCC received a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
| FG001 | Cohort 2: HCC-Systemic Therapy Naïve | Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All allocated participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: HCC-Prior Systemic Therapy With Sorafenib | Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Objective Response Rate (ORR) | ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target and non-target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented. | All participants who received at least one dose of study treatment during the first course of therapy. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
Up to approximately 87 months
All-cause mortality (ACM)=all allocated participants; AEs=all participants who received ≥1 dose of treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression (NP), malignant NP, and disease progression not related to treatment were excluded. Per protocol, collection of AEs and ACM were planned for both first and second courses and reported separately.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: Hepatocellular Carcinoma (HCC)-Prior Systemic Therapy With Sorafenib-First Course | Participants with previously systemically treated HCC received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system 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 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 24, 2022 | Aug 1, 2024 | Prot_SAP_001.pdf |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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|
| Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Disease Control Rate (DCR) | DCR was defined as the percentage of participants who had a CR (disappearance of all target and non-target lesions), PR (at least a 30% decrease in the sum of diameters of target and non-target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions.]). CR, PR, and SD were evaluated per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. Participants with missing data were considered as participants whose disease was not under control. The percentage of participants who experienced a confirmed CR, PR, or SD is reported. | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Time to Progression (TTP) | TTP was defined as the time from the first dose to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. The TTP was analyzed using the product-limit (Kaplan-Meier) method for censored data. TTP per RECIST 1.1 is presented. | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Progression-Free Survival (PFS) | PFS was defined as the time from the first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. PFS is presented. | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Overall Survival (OS) | OS was determined for all participants and was defined as the time from the first dose to death due to any cause. Participants were censored at the last known alive date. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. The OS is presented. | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be 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 is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experienced at least one AE is presented. Per protocol, final analysis for this outcome measure was planned to be performed during the first course of therapy only. | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be 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 is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who discontinued study treatment due to an AE is presented. Per protocol, final analysis for this outcome measure was planned to be performed during the first course of therapy only. | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
| Zhou X, Cao J, Topatana W, Xie T, Chen T, Hu J, Li S, Juengpanic S, Lu Z, Zhang B, Wang K, Feng X, Shen J, Chen M. Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis. Immunotherapy. 2023 Apr;15(5):353-365. doi: 10.2217/imt-2022-0168. Epub 2023 Feb 27. |
| 35421228 | Derived | Verset G, Borbath I, Karwal M, Verslype C, Van Vlierberghe H, Kardosh A, Zagonel V, Stal P, Sarker D, Palmer DH, Vogel A, Edeline J, Cattan S, Kudo M, Cheng AL, Ogasawara S, Daniele B, Chan SL, Knox JJ, Qin S, Siegel AB, Chisamore M, Hatogai K, Wang A, Finn RS, Zhu AX. Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Clin Cancer Res. 2022 Jun 13;28(12):2547-2554. doi: 10.1158/1078-0432.CCR-21-3807. |
| 35364421 | Derived | Kudo M, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer DH, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Yau T, Gurary EB, Siegel AB, Wang A, Cheng AL, Zhu AX; KEYNOTE-224 Investigators. Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Eur J Cancer. 2022 May;167:1-12. doi: 10.1016/j.ejca.2022.02.009. Epub 2022 Mar 29. |
| 29875066 | Derived | Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3. |
| Withdrawal by Subject |
|
| Protocol Violation |
|
| Sponsor Decision |
|
| BG001 | Cohort 2: HCC-Systemic Therapy Naïve | Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Cohort 2: HCC-Systemic Therapy Naïve | Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. |
|
|
| Secondary | Duration of Response (DOR) | DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target and non-target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target and non-target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed, started a new anti-cancer therapy, been lost to follow-up, or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. The DOR per RECIST 1.1 for all participants who had a confirmed CR or PR is presented. | All participants who received at least one dose of study treatment and who had a confirmed CR or confirmed PR during the first course of therapy. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
|
|
| Secondary | Disease Control Rate (DCR) | DCR was defined as the percentage of participants who had a CR (disappearance of all target and non-target lesions), PR (at least a 30% decrease in the sum of diameters of target and non-target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions.]). CR, PR, and SD were evaluated per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. Participants with missing data were considered as participants whose disease was not under control. The percentage of participants who experienced a confirmed CR, PR, or SD is reported. | All participants who received at least one dose of study treatment during the first course of therapy. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
|
|
| Secondary | Time to Progression (TTP) | TTP was defined as the time from the first dose to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. If there was no documented disease progression, TTP was censored at last tumor assessment date. The TTP was analyzed using the product-limit (Kaplan-Meier) method for censored data. TTP per RECIST 1.1 is presented. | All participants who received at least one dose of study treatment during the first course of therapy. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
|
|
| Secondary | Progression-Free Survival (PFS) | PFS was defined as the time from the first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded central imaging vendor. PD was at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm, OR unequivocal progression for non-target lesions, OR appearance of one or more new lesions. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. PFS is presented. | All participants who received at least one dose of study treatment during the first course of therapy. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
|
|
| Secondary | Overall Survival (OS) | OS was determined for all participants and was defined as the time from the first dose to death due to any cause. Participants were censored at the last known alive date. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. The OS is presented. | All participants who received at least one dose of study treatment during the first course of therapy. | Posted | Median | 95% Confidence Interval | Months | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
|
|
| Secondary | Number of Participants Who Experienced At Least One Adverse Event (AE) | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be 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 is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experienced at least one AE is presented. Per protocol, final analysis for this outcome measure was planned to be performed during the first course of therapy only. | All participants who received at least one dose of study treatment during the first course of therapy. | Posted | Count of Participants | Participants | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
|
|
| Secondary | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be 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 is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who discontinued study treatment due to an AE is presented. Per protocol, final analysis for this outcome measure was planned to be performed during the first course of therapy only. | All participants who received at least one dose of study treatment during the first course of therapy. | Posted | Count of Participants | Participants | Up to approximately 34 months for Cohort 1 and up to approximately 28 months for Cohort 2 |
|
|
|
| 94 |
| 105 |
| 44 |
| 104 |
| 96 |
| 104 |
| EG001 | Cohort 2: HCC-Systemic Therapy Naïve-First Course | Participants with HCC who had not received treatment for systemic disease received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 35 administrations. Participants who stopped pembrolizumab as a result of obtaining a confirmed complete response (CR) or those who stopped after receiving 35 trial treatments were eligible for an additional 17 trial treatments (approximately an additional 1 year of treatment) after progressive disease if they met the criteria for re-treatment. | 42 | 51 | 21 | 51 | 46 | 51 |
| EG002 | Cohort 1: Hepatocellular Carcinoma (HCC)-Prior Systemic Therapy With Sorafenib-Second Course | Participants from Cohort 1 who met the criteria for re-treatment received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 17 administrations. | 2 | 4 | 0 | 4 | 4 | 4 |
| EG003 | Cohort 2: HCC-Systemic Therapy Naïve-Second Course | Participants from Cohort 2 who met the criteria for re-treatment received a pembrolizumab 200 mg IV infusion on Day 1 of each 3-week cycle for up to 17 administrations. | 0 | 1 | 0 | 1 | 0 | 1 |
| Acute myocardial infarction | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Atrioventricular block second degree | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Cardiogenic shock | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Chronic left ventricular failure | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Myocarditis | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Ventricular fibrillation | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypophysitis | Endocrine disorders | MedDRA 26.0 | Systematic Assessment |
|
| Retinal vein occlusion | Eye disorders | MedDRA 26.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Autoimmune colitis | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Gastritis haemorrhagic | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Umbilical hernia | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Varices oesophageal | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Death | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Multiple organ dysfunction syndrome | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Ulcer haemorrhage | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hepatic cytolysis | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hepatic failure | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hepatic haemorrhage | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Immune-mediated hepatitis | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Large intestine infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Pneumonia bacterial | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Hip fracture | 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 |
|
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Diabetic metabolic decompensation | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
|
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
|
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
|
| Tumour necrosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Radiculopathy | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Lichenoid keratosis | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypovolaemic shock | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA 26.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Varices oesophageal | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Serum ferritin decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
|
| Vitamin D deficiency | 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 |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Night sweats | 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 |
|
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.
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |