Interventional Oncology: Chemoembolization

LEAP-012 Trial in Progress: Pembrolizumab, Lenvatinib, and Transarterial Chemoembolization Combination Therapy for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment

Tuesday, March 23, 2021

10:50 AM – 10:59 AM ET

Presenting Author(s)

DM

David Madoff, MD

Professor of Radiology & Biomedical Imaging

Author/Co-author(s)

JL

Josep M. Llovet, MD, PhD

Professor of Medicine
AE

Anthony B. El-Khoueiry, MD

Associate Professor of Clinical Medicine
MK

Masatoshi Kudo, MD, PhD

Professor and Chairman Department of Gastroenterology and Hepatology
RF

Richard Finn, MD

Professor of Medicine
SO

Sadahisa Ogasawara, MD, PhD

Associate Professor
ZR

Zhenggang Ren, PhD

Department of Liver Surgery
KM

Kalgi Mody, MD

Director, Oncology Clinical Research
JL

Jerry J. Li, PhD

Medical Oncology
AS

Abby B. Siegel, MD

Medical Oncology
LD

Leonid Dubrovsky, MD

Medical Oncology
AV

Arndt Vogel, MD, PhD

Professor of Gastrointestinal Oncology

Purpose: Limited treatment options are available for patients with intermediate hepatocellular carcinoma (HCC). Lenvatinib, a potent multikinase inhibitor, and pembrolizumab, a programmed death receptor-1 blocking antibody, are approved first- and second-line therapies for advanced HCC, respectively. LEAP-012 (NCT04246177) is investigating lenvatinib plus pembrolizumab in combination with transarterial chemoembolization (TACE) versus placebo plus TACE in patients with intermediate HCC.

Materials and Methods: LEAP-012 is a randomized double-blind phase 3 study. Adults with confirmed HCC localized to the liver without portal vein thrombosis and not amenable to curative treatment, ≥1 measurable lesion per RECIST v1.1, Eastern Cooperative Oncology Group performance status of 0 or 1, and no previous treatment with locoregional therapy or systemic chemotherapy for HCC are eligible. Patients will be randomly assigned to receive lenvatinib 8 (body weight < 60 kg) or 12 mg (body weight ≥60 kg) orally once daily plus pembrolizumab 400 mg intravenously every 6 weeks (Q6W) plus TACE or placebo orally once daily plus placebo intravenously Q6W, plus TACE. Response will be assessed by imaging every 9 weeks, and safety will be assessed throughout the study and up to 90 days after the end of treatment. Coprimary end points are overall survival and progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and time to progression (TTP) per modified RECIST by BICR; ORR, DCR, DOR, and TTP per RECIST v1.1 by BICR; and safety. Exploratory end points are PFS, ORR, DCR, DOR, TTP, and time from randomization to second/subsequent progression per RECIST v1.1 by investigator review, identification of molecular biomarkers, and health-related quality of life.

Results: Recruitment began in April 2020. The planned sample size is 950 patients.

Conclusion: LEAP-012 will elucidate the clinical benefit of adding lenvatinib plus pembrolizumab to the current standard of care TACE for patients with intermediate-stage HCC not amenable to curative treatment.

Table Builder:

References: