Hepatocellular CarcinomaPhase 3NCT02702401
Study of Pembrolizumab (MK-3475) vs. Best Supportive Care in Participants With Previously Systemically Treated Advanced Hepatocellular Carcinoma (MK-3475-240/KEYNOTE-240)
A Phase 3 study testing Pembrolizumab in people with Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC.
Trial summary
This is a study of pembrolizumab (MK-3475) in participants with previously systemically treated advanced hepatocellular carcinoma (HCC). The primary objectives of this study are to determine 1) Progression-Free Survival (PFS) and 2) Overall Survival (OS) of pembrolizumab plus best supportive care (BSC) compared with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 413 participants
- Where
- No sites listed yet
- Study dates
- 26 May 2016to 22 Sep 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a HCC diagnosis confirmed by radiology, histology or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
- Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach.
- Has a Child-Pugh Class A liver score within 7 days of first dose of study drug.
- Has a predicted life expectancy >3 months.
- Has at least one measurable lesion based on RECIST 1.1 as confirmed by the blinded central imaging vendor.
- Has a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 7 days of first dose of study drug.
Show all 11Show fewer
- Has documented objective radiographic progression during or after treatment with sorafenib or intolerance to sorafenib.
- Participants with chronic infection by Hepatitis C Virus (HCV) who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, participants with successful HCV treatment are allowed as long as there are ≥4 weeks between achieving sustained viral response (SVR12) and start of study drug.
- Has controlled Hepatitis B Virus (HBV) infection.
- Is willing to use an adequate method of contraception for the course of the study through at least 120 days or longer based on local regulation after the last dose of study drug (male and female participants of childbearing potential).
- Demonstrates adequate organ function.
Who cannot join
- Is currently participating, or has participated in a study of an investigational agent and received study drug, herbal/complementary oral or IV medicine, or used an investigational device within 4 weeks of the first dose of study drug. Participants must also have recovered from associated therapy (i.e., to Grade ≤1 or baseline) and from adverse events (AEs) due to any prior therapy.
- Has received sorafenib within 14 days of first dose of study drug.
- Has had esophageal or gastric variceal bleeding within the last 6 months.
- Has clinically apparent ascites on physical examination. Note: ascites detectable on imaging studies only ARE allowed.
- Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
- Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
Show all 25Show fewer
- Has had a solid organ or hematologic transplant.
- Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib, prior to the start of study drug.
- Has a known severe hypersensitivity (≥Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study drug.
- Has had major surgery to liver or other site within 4 weeks prior to the first dose of study drug.
- Has had minor surgery (i.e., simple excision, tooth extraction) ≤7 days prior to the first dose of study drug (Cycle 1, Day 1).
- Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to starting study drug.
- Has a diagnosed additional malignancy within 3 years prior to first dose of study drug with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers.
- Has known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has a history of non-infectious pneumonitis that required steroids or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the first dose of study drug through 120 days or longer based on local regulation after the last dose of study drug.
- Has received prior immunotherapy including anti-programmed cell death-1 (anti-PD-1), anti-PD-ligand-1 (anti-PD-L1), or anti-PD-L2 agents, or if the participant has previously participated in Merck pembrolizumab (MK-3475) studies.
- Has a known history of human immunodeficiency virus (HIV).
- Has dual active HBV infection and HCV infection at study entry.
- Has received a live vaccine within 30 days of planned start of study drug (Cycle 1, Day 1).
About this study
Official title: A Phase III Study of Pembrolizumab (MK-3475) vs. Best Supportive Care as Second-Line Therapy in Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-240)
This is a study of pembrolizumab (MK-3475) in participants with previously systemically treated advanced hepatocellular carcinoma (HCC).
The primary objectives of this study are to determine 1) Progression-Free Survival (PFS) and 2) Overall Survival (OS) of pembrolizumab plus best supportive care (BSC) compared with placebo plus BSC. The primary hypotheses of this study are: 1) pembrolizumab plus BSC prolongs PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, assessed by Blinded Independent Central Review compared to placebo plus BSC, and 2) pembrolizumab plus BSC improves OS compared with placebo plus BSC.
Effective with Amendment 4: Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Pembrolizumab, Placebo, Best Supportive Care
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
- Medical subject headings
- Carcinoma, Hepatocellular, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
IV infusion
PlaceboDrug
0.90% w/v sodium chloride IV infusion
Best Supportive CareOther
Best supportive care will include pain management and management of other potential complications including ascites per local standards of care.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab+Best Supportive Care | Experimental | Participants receive a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year). Receives: Biological: Pembrolizumab; Other: Best Supportive Care |
| Placebo+Best Supportive Care | Placebo comparator | Participants receive a placebo IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Receives: Drug: Placebo; Other: Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. 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. Final analyses for PFS was performed for the first pembrolizumab course at protocol specified cut off of 26-Mar-2018.
Measured: Through database cutoff date of 26-Mar-2018 (Up to approximately 21 months)
Overall Survival (OS)
OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for OS was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
Measured: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Secondary outcomes (6)
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The ORR was analyzed using the Miettinen \& Nurminen method. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented. Final analyses for ORR was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
Measured: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
DCR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions), Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), or Stable Disease (SD) per RECIST 1.1 after ≥6 weeks as assessed by Blinded Independent Central Review (BICR). The DCR was analyzed using the Miettinen \& Nurminen method. The percentage of participants who experienced a CR, PR, or SD is presented. Final analyses for DCR was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
Measured: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Time to Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. 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 for all participants. Final analyses for TTP was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
Measured: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
DOR was determined in participants who demonstrated a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. The DOR was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for DOR was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
Measured: From time of first documented evidence of CR or PR through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Number of Participants Who Experienced At Least One Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. Final analyses for AE was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
Measured: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. Final analyses for AE was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
Measured: From Day 1 through end of treatment (Up to approximately 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2016 (estimated)
- Study start26 May 2016
- Primary completion2 Jan 2019
- Study completion22 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 413 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02702401
- Sponsor's protocol ID
- 3475-240
- Other IDs
- 163456, MK-3475-240, KEYNOTE-240, 2015-004567-36, 2015
- Status last verified
- Aug 2022
- First submitted
- 3 Mar 2016
- Last updated
- 29 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. doi: 10.1200/JCO.19.01307. Epub 2019 Dec 2.
PubMed 31790344Chan 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.
PubMed 41453647Finn RS, Gu K, Chen X, Merle P, Lee KH, Bouattour M, Cao P, Wang W, Cheng AL, Zhu L, Lim HY, Kudo M, Pan Y, Chang TT, Edeline J, Li W, Yang P, Li C, Li J, Siegel AB, Qin S. Second-line pembrolizumab for advanced HCC: Meta-analysis of the phase III KEYNOTE-240 and KEYNOTE-394 studies. JHEP Rep. 2025 Feb 4;7(6):101350. doi: 10.1016/j.jhepr.2025.101350. eCollection 2025 Jun.
PubMed 40486134Vogel A, Merle P, Verslype C, Finn RS, Zhu AX, Cheng AL, Chan SL, Yau T, Ryoo BY, Knox J, Daniele B, Qin S, Wei Z, Miteva Y, Malhotra U, Siegel AB, Kudo M. ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240. Ther Adv Med Oncol. 2021 Sep 30;13:17588359211039928. doi: 10.1177/17588359211039928. eCollection 2021.
PubMed 34616489
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study of Pembrolizumab (MK-3475) vs. Best Supportive Care as Second-Line Therapy in Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-240)
- ClinicalTrials.gov ID
- NCT02702401
- Acronym / sponsor ID
- 3475-240
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 413 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 26 May 2016 (actual)
- Primary completion
- 2 Jan 2019 (actual)
- Study completion
- 22 Sep 2021 (actual)
- First posted
- 8 Mar 2016 (estimated)
- Results
- Posted 17 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study of pembrolizumab (MK-3475) in participants with previously systemically treated advanced hepatocellular carcinoma (HCC).
The primary objectives of this study are to determine 1) Progression-Free Survival (PFS) and 2) Overall Survival (OS) of pembrolizumab plus best supportive care (BSC) compared with placebo plus BSC. The primary hypotheses of this study are: 1) pembrolizumab plus BSC prolongs PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, assessed by Blinded Independent Central Review compared to placebo plus BSC, and 2) pembrolizumab plus BSC improves OS compared with placebo plus BSC.
Effective with Amendment 4: Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab+Best Supportive Care | Experimental | Biological: Pembrolizumab, Other: Best Supportive CareParticipants receive a pembrolizumab 200 mg intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year). |
| Placebo+Best Supportive Care | Placebo comparator | Drug: Placebo, Other: Best Supportive CareParticipants receive a placebo IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment PLUS BSC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Has a HCC diagnosis confirmed by radiology, histology or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
- Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach.
- Has a Child-Pugh Class A liver score within 7 days of first dose of study drug.
- Has a predicted life expectancy >3 months.
- Has at least one measurable lesion based on RECIST 1.1 as confirmed by the blinded central imaging vendor.
Key exclusion criteria (25 listed)
- Is currently participating, or has participated in a study of an investigational agent and received study drug, herbal/complementary oral or IV medicine, or used an investigational device within 4 weeks of the first dose of study drug. Participants must also have recovered from associated therapy (i.e., to Grade ≤1 or baseline) and from adverse events (AEs) due to any prior therapy.
- Has received sorafenib within 14 days of first dose of study drug.
- Has had esophageal or gastric variceal bleeding within the last 6 months.
- Has clinically apparent ascites on physical examination. Note: ascites detectable on imaging studies only ARE allowed.
- Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475, KEYTRUDA®IV infusion | Biological | Pembrolizumab+Best Supportive Care |
| Placebo0.90% w/v sodium chloride IV infusion | Drug | Placebo+Best Supportive Care |
| Best Supportive CareBest supportive care will include pain management and management of other potential complications including ascites per local standards of care. | Other | Pembrolizumab+Best Supportive Care, Placebo+Best Supportive Care |
Primary outcome
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Through database cutoff date of 26-Mar-2018 (Up to approximately 21 months)
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 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesion was also considered PD. 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. Final analyses for PFS was performed for the first pembrolizumab course at protocol specified cut off of 26-Mar-2018.
Overall Survival (OS)
Time frame: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Final analyses for OS was performed for the first pembrolizumab course at protocol specified cut off of 02-Jan-2019.
6 secondary outcomes
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Time to Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: From time of first documented evidence of CR or PR through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Number of Participants Who Experienced At Least One Adverse Event (AE)
Time frame: Through database cutoff date of 02-Jan-2019 (Up to approximately 30 months)
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time frame: From Day 1 through end of treatment (Up to approximately 24 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31790344Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. doi: 10.1200/JCO.19.01307. Epub 2019 Dec 2.
- Derived from this study: PubMed 41453647Chan 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.
- Derived from this study: PubMed 40486134Finn RS, Gu K, Chen X, Merle P, Lee KH, Bouattour M, Cao P, Wang W, Cheng AL, Zhu L, Lim HY, Kudo M, Pan Y, Chang TT, Edeline J, Li W, Yang P, Li C, Li J, Siegel AB, Qin S. Second-line pembrolizumab for advanced HCC: Meta-analysis of the phase III KEYNOTE-240 and KEYNOTE-394 studies. JHEP Rep. 2025 Feb 4;7(6):101350. doi: 10.1016/j.jhepr.2025.101350. eCollection 2025 Jun.
- Derived from this study: PubMed 34616489Vogel A, Merle P, Verslype C, Finn RS, Zhu AX, Cheng AL, Chan SL, Yau T, Ryoo BY, Knox J, Daniele B, Qin S, Wei Z, Miteva Y, Malhotra U, Siegel AB, Kudo M. ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240. Ther Adv Med Oncol. 2021 Sep 30;13:17588359211039928. doi: 10.1177/17588359211039928. eCollection 2021.
- Merck Oncology Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pembrolizumab in people with Hepatocellular Carcinoma, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (time frame: Through database cutoff date of 26-Mar-2018 (Up to approximately 21 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02702401, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022.