Last reviewed · How we verify
Study of Pembrolizumab (MK-3475) or Placebo Given With Best Supportive Care in Asian Participants With Previously Treated Advanced Hepatocellular Carcinoma (MK-3475-394/KEYNOTE-394)
Phase 3 trial testing pembrolizumab in Carcinoma, Hepatocellular in 453 participants. Completed in 15 October 2024.
| Lead sponsor | Merck Sharp & Dohme LLC |
|---|---|
| Phase | Phase 3 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | randomized |
| Design | parallel |
| Masking | double |
| Primary purpose | treatment |
| Enrollment | 453 |
| Start date | 27 April 2017 |
| Primary completion | 30 June 2021 |
| Estimated completion | 15 October 2024 |
| Sites | 41 locations across Hong Kong, Malaysia, Taiwan, South Korea, China |
Merck Sharp & Dohme LLC — full company profile →
18 and older, any sex, with Carcinoma, Hepatocellular. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
OS is the time from randomization to death due to any cause, based on the Kaplan-Meier method for censored data.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 14.6 | 12.6 – 18.0 |
| Placebo + BSC | 13.0 | 10.5 – 15.1 |
PFS is the time from randomization to first documented disease progression or death due to any cause per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) based on the Kaplan-Meier method for censored data.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 2.6 | 1.5 – 2.8 |
| Placebo + BSC | 2.3 | 1.4 – 2.8 |
ORR is the percentage of participants who achieve complete response (CR) or partial response (PR) with confirmation per RECIST 1.1 by BICR. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 12.7 | 9.1 – 17.0 |
| Placebo + BSC | 1.3 | 0.2 – 4.6 |
DOR is the time from first documented evidence of CR or PR per RECIST 1.1 by BICR until disease progression per RECIST 1.1 by BICR or death, based on Kaplan-Meier method for censored data. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 23.9 | 2.6 – 44.4 |
| Placebo + BSC | 5.6 | 3.0 – 5.6 |
DCR is the percentage of participants who achieve CR, PR, or stable disease (SD) for ≥5 weeks prior to evidence of disease progression per RECIST 1.1 by BICR. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 52.7 | 46.8 – 58.4 |
| Placebo + BSC | 47.7 | 39.6 – 55.9 |
TTP is the time from randomization to first documented disease progression per RECIST 1.1 by BICR, based on Kaplan-Meier method for censored data.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 2.7 | 1.5 – 2.8 |
| Placebo + BSC | 1.7 | 1.4 – 2.8 |
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 283 | |
| Placebo + BSC | 147 |
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.
| Group | Value | 95% CI |
|---|---|---|
| Pembrolizumab + BSC | 38 | |
| Placebo + BSC | 13 |
Time frame: All-cause mortality: from randomization up to approximately 7 years. Adverse events: from first treatment up to approximately 7 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Pembrolizumab First Course | Placebo First Course | Pembrolizumab Second Course |
|---|---|---|---|---|
| Blood bilirubin increased | Investigations | — | — | — |
| Aspartate aminotransferase increased | Investigations | — | — | — |
| Ascites | Gastrointestinal disorders | — | — | — |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | — | — | — |
| Pneumonia | Infections and infestations | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — |
| Autoimmune hepatitis | Hepatobiliary disorders | — | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — | — |
| Pyrexia | General disorders | — | — | — |
| Hepatic encephalopathy | Nervous system disorders | — | — | — |
| Anaemia | Blood and lymphatic system disorders | — | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — | — |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | — | — | — |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — |
| Hepatic failure | Hepatobiliary disorders | — | — | — |
| Hepatitis E | Infections and infestations | — | — | — |
| Influenza | Infections and infestations | — | — | — |
| Sepsis | Infections and infestations | — | — | — |
| Upper respiratory tract infection | Infections and infestations | — | — | — |
| Decreased appetite | Metabolism and nutrition disorders | — | — | — |
| Hyponatraemia | Metabolism and nutrition disorders | — | — | — |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | — | — | — |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | — | — | — |
| Acute myocardial infarction | Cardiac disorders | — | — | — |
| Reaction | System | Pembrolizumab First Course | Placebo First Course | Pembrolizumab Second Course |
|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — |
| Blood bilirubin increased | Investigations | — | — | — |
| Platelet count decreased | Investigations | — | — | — |
| Gamma-glutamyltransferase increased | Investigations | — | — | — |
| Pyrexia | General disorders | — | — | — |
| White blood cell count decreased | Investigations | — | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — | — |
| Anaemia | Blood and lymphatic system disorders | — | — | — |
| Decreased appetite | Metabolism and nutrition disorders | — | — | — |
| Rash | Skin and subcutaneous tissue disorders | — | — | — |
| Blood alkaline phosphatase increased | Investigations | — | — | — |
| Neutrophil count decreased | Investigations | — | — | — |
| Hypoalbuminaemia | Metabolism and nutrition disorders | — | — | — |
| Pruritus | Skin and subcutaneous tissue disorders | — | — | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — | — | — |
| Upper respiratory tract infection | Infections and infestations | — | — | — |
| Proteinuria | Renal and urinary disorders | — | — | — |
| Lymphocyte count decreased | Investigations | — | — | — |
| Hypothyroidism | Endocrine disorders | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — |
| Arthralgia | Musculoskeletal and connective tissue disorders | — | — | — |
| Weight decreased | Investigations | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — | — |
| Bilirubin conjugated increased | Investigations | — | — | — |
| Insomnia | Psychiatric disorders | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — |
| Fatigue | General disorders | — | — | — |
| Hyponatraemia | Metabolism and nutrition disorders | — | — | — |
| Asthenia | General disorders | — | — | — |
| Hypertension | Vascular disorders | — | — | — |
| Abdominal distension | Gastrointestinal disorders | — | — | — |
| Abdominal pain upper | Gastrointestinal disorders | — | — | — |
| Hyperglycaemia | Metabolism and nutrition disorders | — | — | — |
| Hypokalaemia | Metabolism and nutrition disorders | — | — | — |
| Hypoproteinaemia | Metabolism and nutrition disorders | — | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — | — |
| Hyperthyroidism | Endocrine disorders | — | — | — |
| Ascites | Gastrointestinal disorders | — | — | — |
Most-reported serious reactions: Blood bilirubin increased, Aspartate aminotransferase increased, Ascites, Upper gastrointestinal haemorrhage, Pneumonia, Alanine aminotransferase increased, Autoimmune hepatitis, Diarrhoea.
Data from ClinicalTrials.gov NCT03062358 adverse events section.
The purpose of this study is to determine the efficacy and safety of pembrolizumab or placebo given with best supportive care (BSC) in Asian participants with previously systemically treated advanced hepatocellular carcinoma (HCC). The primary hypothesis of this study is that overall survival is prolonged in participants who receive pembrolizumab compared to those who receive placebo.
8 peer-reviewed publications reference this trial (live from Europe PMC):
Verify or expand the search:
Trials testing the same drug.
Currently open trials in the same condition.
Trials by the same sponsor.
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03062358.
Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing