Clinical Trials/NCT03062358

NCT03062358

Completed

Phase 3

A Phase III Randomized Double-blind Study of Pembrolizumab Plus Best Supportive Care vs. Placebo Plus Best Supportive Care as Second-Line Therapy in Asian Subjects With Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-394)

Merck Sharp & Dohme LLC41 sites in 5 countries453 target enrollmentApril 27, 2017

ConditionsCarcinoma, Hepatocellular

Interventionspembrolizumab best supportive care (BSC)placebo

Drugspembrolizumab placebo

Overview

Phase: Phase 3
Intervention: pembrolizumab
Conditions: Carcinoma, Hepatocellular
Sponsor: Merck Sharp & Dohme LLC
Enrollment: 453
Locations: 41
Primary Endpoint: Overall Survival (OS)
Status: Completed
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

April 27, 2017

End Date

October 15, 2024

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Merck Sharp & Dohme LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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 A liver score within 7 days prior to first dose of study medication
•Has a life expectancy of \>3 months
•Has at least one measurable lesion based on RECIST version 1.1 as determined by investigator.
•Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 7 days prior to receiving the first dose of study medication.
•Has documented objective radiographic progression during or after treatment with sorafenib or oxaliplatin-based chemotherapy, or else intolerance to sorafenib or oxaliplatin-based chemotherapy
•Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
•Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication

Exclusion Criteria

•Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study medication
•Has received sorafenib or oxaliplatin-based chemotherapy within 14 days of first dose of study medication
•Has had esophageal or gastric variceal bleeding within the last 6 months
•Has clinically apparent ascites on physical examination
•Has portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
•Has had clinically diagnosed hepatic encephalopathy in the last 6 months
•Has had a solid organ or hematologic transplant
•Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib or oxaliplatin-based chemotherapy, prior to start of study medication
•Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
•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 medication

Arms & Interventions

pembrolizumab + BSC

Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Intervention: pembrolizumab

pembrolizumab + BSC

Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Intervention: best supportive care (BSC)

placebo + BSC

Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Intervention: placebo

placebo + BSC

Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Intervention: best supportive care (BSC)

Outcomes

Primary Outcomes

Overall Survival (OS)

Time Frame: Up to approximately 4 years

OS is the time from randomization to death due to any cause, based on the Kaplan-Meier method for censored data.

Secondary Outcomes

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
Duration Of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
Number of Participants Who Experienced At Least One Adverse Event (AE)(Up to approximately 30 months.)
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)
Number of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 27 months.)
Time To Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 4 years)