Study 116 is an ongoing phase Ib multicenter open-label study of lenvatinib plus pembrolizumab in patients with uHCC. The study consists of 2 phases: a dose-limiting toxicity (DLT) phase and an expansion phase. Patients received lenvatinib 12 mg (if bodyweight ≥ 60 kg) or 8 mg (if bodyweight < 60 kg) orally once daily and pembrolizumab 200 mg intravenously on day 1 of a 21-day treatment cycle (for up to 2 years after cycle 1 day 1). If no DLTs were reported in the DLT phase, the expansion phase would be initiated using the recommended dose from the DLT phase. Treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of consent. Additional details regarding continued pembrolizumab treatment are provided in the Appendix (online only).
Key inclusion criteria comprised the following: histologically or cytologically confirmed HCC (excluding fibrolamellar, sarcomatoid, and mixed cholangio-HCC tumors) or clinically confirmed HCC according to the American Association for the Study of Liver Diseases criteria; stage B (not suitable for transarterial chemoembolization) or C categorization based on the Barcelona Clinic Liver Cancer (BCLC) staging system; at least 1 measurable target lesion according to mRECIST per investigator assessment; Child-Pugh class A (score, 5-6); and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Patients were excluded if they had clear invasion of the bile duct (classified clinically as a cholestatic type of HCC in which a patient’s initial manifestation is obstructive jaundice resulting from tumor thrombosis/compression/diffuse infiltration into the biliary tract); portal vein invasion with Vp426 (link); prior blood-enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production [eg, granulocyte colony-stimulating factor]) within 28 days before first dose of study drugs; prior treatment with lenvatinib or any anti–PD-1, anti–PD-L1, or anti–PD-L2 agent; and imaging findings with HCC having ≥ 50% liver occupation. Additionally, patients were excluded from the expansion phase if they had received prior systemic therapy for uHCC.
Written informed consent was provided by all patients before undergoing any study-specific procedures. The study protocol was approved by the relevant institutional review boards/independent ethics committees, and the study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines.
Key inclusion criteria comprised the following: histologically or cytologically confirmed HCC (excluding fibrolamellar, sarcomatoid, and mixed cholangio-HCC tumors) or clinically confirmed HCC according to the American Association for the Study of Liver Diseases criteria; stage B (not suitable for transarterial chemoembolization) or C categorization based on the Barcelona Clinic Liver Cancer (BCLC) staging system; at least 1 measurable target lesion according to mRECIST per investigator assessment; Child-Pugh class A (score, 5-6); and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Patients were excluded if they had clear invasion of the bile duct (classified clinically as a cholestatic type of HCC in which a patient’s initial manifestation is obstructive jaundice resulting from tumor thrombosis/compression/diffuse infiltration into the biliary tract); portal vein invasion with Vp426 (link); prior blood-enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production [eg, granulocyte colony-stimulating factor]) within 28 days before first dose of study drugs; prior treatment with lenvatinib or any anti–PD-1, anti–PD-L1, or anti–PD-L2 agent; and imaging findings with HCC having ≥ 50% liver occupation. Additionally, patients were excluded from the expansion phase if they had received prior systemic therapy for uHCC.
Written informed consent was provided by all patients before undergoing any study-specific procedures. The study protocol was approved by the relevant institutional review boards/independent ethics committees, and the study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines.
