Phase 3 Study of Pembrolizumab and Lenvatinib in Combination with TACE for Incurable/Non-metastatic Hepatocellular Carcinoma

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 950

Inclusion Criteria

1.Has a diagnosis of HCC confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
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 180 days post TACE or 30 days after the last dose of lenvatinib/oral placebo, whichever occurs last:
-Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
-Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).
-Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
-Male participants must agree to refrain from donating sperm for 180 days after TACE.
11.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
-Is not a WOCBP OR
-Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days post TACE, 120 days post pembrolizumab/IV placebo or 30 days post lenvatinib/oral placebo, whichever occurs last. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
-A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
-If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
·The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
·Contraceptive use by women should be consistent with local regulations regardin

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 factor X inhibitors or 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).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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