Incurable/Non-metastatic Hepatocellular Carcinoma MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Has a diagnosis of HCC confirmed by radiology, histology, or cytology. Has a radiologic diagnosis of HCC as per the AASLD guidelines, which requires: -liver cirrhosis and a liver mass confirmed by BICR that shows arterial phase hyperenhancement on triphasic CT or MRI, AND EITHER: Is =20 mm with either non-peripheral portal washout or an enhancing capsule OR Is 10-19 mm with non-peripheral portal venous washout AND an enhancing capsule. 2.Has HCC localized to the liver without portal vein thrombosis, and not amenable to curative treatment such as resection, ablation, or liver transplant. No extrahepatic HCC is permitted, confirmed by BICR. 3.Has at least one measurable HCC lesion based on RECIST 1.1, confirmed by BICR. 4.Has all lesions treatable with TACE in 1 or 2 sessions. 5.Is amenable, without any contraindications, to the TACE procedure and chemotherapy agent pre specified at the study site. 6.Has a CP class A liver score within 7 days prior to first dose of study intervention. 7.Has a predicted life expectancy of >3 months. 8.Has an ECOG PS of 0 to 1 within 7 days prior to first dose of study intervention. 9.Is male or female = 18 years of age at the time of signing the informed consent. 10.Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Lenvatinib 7 days - TACE 95 days Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 270 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: 1.Has HCC lesion(s) measuring =10 cm in any dimension, has more than 10 lesions on radiographic evaluation or has HCC lesions occupying =50% of the liver volume, confirmed by BICR. 2.Has had esophageal or gastric variceal bleeding within the last 6 months. 3.Has bleeding or thrombotic disorders or is using anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Treatment with antiplatelet agents and low molecular weight heparin is permitted. 4.Has clinically apparent ascites on physical examination that is not controlled with medication. Ascites detectable on imaging studies only is allowed. 5.Has any macrovascular tumor thrombosis in the portal veins, confirmed by BICR. Microvascular tumor thrombosis detected on biopsy, but not radiographic scan, is permitted. 6.Has had clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy. Participants on rifaximin or lactulose during screening to control their hepatic encephalopathy are excluded. 7.Has received any systemic chemotherapy, including anti-VEGF therapy, or any systemic investigational anticancer agents for HCC. 8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare pembrolizumab plus lenvatinib in combination with transarterial chemoembolization (TACE) versus placebo plus TACE with regard to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by blinded, independent central review (BICR). 2. To compare pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE with regard to overall survival (OS). ;Secondary Objective: 1. To evaluate pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE with regard to PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and time to progression (TTP) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) assessed by BICR. 2. To evaluate the safety and tolerability of pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE. 3. To evaluate pembrolizumab plus lenvatinib in combination with TACE versus placebo plus TACE with regard to efficacy outcomes per RECIST 1.1 assessed by BICR. ;Primary end point(s): 1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 2. Overall Survival (OS) ;Timepoint(s) of evaluation of this end point: 1. Up to ~43 months 2. Up to ~95 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) 2. Objective Response Rate (ORR) per mRECIST 3. Disease Control Rate (DCR) per mRECIST 4. Duration of Response (DOR) per mRECIST 5. Time to Progression (TTP) per mRECIST 6. Percentage of Participants Who Experience At Least One Adverse Event (AE) 7. Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE) 8. Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI) 9. Percentage of Participants Who Discontinue Study Drug Due to an AE 10. ORR per RECIST 1.1 11. DCR per RECIST 1.1 12. DOR per RECIST 1.1 13. TTP per RECIST 1.1 ;Timepoint(s) of evaluation of this end point: 1. Up to ~43 months 2. Up to ~95 months 3. Up to ~95 months 4. Up to ~95 months 5. Up to ~95 months 6. Up to ~95 months 7. Up to ~95 months 8. Up to ~95 months 9. Up to ~95 months 10. Up to ~95 months 11. Up to ~95 months 12. Up to ~95 months 13. Up to ~95 months | — |
Countries
Australia, Brazil, Chile, China, Colombia, Denmark, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Portugal, Puerto Rico, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Outcome results
None listed