The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma
Richard S Finn1, Masafumi Ikeda2, Andrew X Zhu34, Max W Sung5, Ari D Baron6, Masatoshi Kudo7, Takuji Okusaka8, Masahiro Kobayashi9, Hiromitsu Kumada9, Shuichi Kaneko10, Marc Pracht11, Konstantin Mamontov12, Tim Meyer13, Tomoki Kubota14, Corina E Dutcus15, Kenichi Saito15, Abby B Siegel16, Leonid Dubrovsky16, Kalgi Mody15, Josep M Llovet1718
Author information
1David Geffen School of Medicine, University of California Los Angeles Medical Center, Los Angeles, CA.
2Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
3Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.
4Jiahui International Cancer Center, Jiahui Health, Shanghai, China.
5Tisch Cancer Institute at Mount Sinai, New York, NY.
6Sutter Health/California Pacific Medical Center Research Institute, San Francisco, CA.
7Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
8Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
9Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
10Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
13Royal Free London National Health Service Foundation Trust, London, United Kingdom.
14Eisai, Tokyo, Japan.
15Eisai, Woodcliff Lake, NJ.
16Merck, Kenilworth, NJ.
17Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
18Liver Cancer Translational Group, Liver Unit, August Pi i Sunyer Biomedical Research Institute Hospital Clinic, University of Barcelona, Catalonia, Spain.
Abstract
Purpose: The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti-PD-1 antibody) in unresectable HCC (uHCC).
Patients and methods: In this open-label multicenter study, patients with uHCC received lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily and pembrolizumab 200 mg intravenously on day 1 of a 21-day cycle. The study included a dose-limiting toxicity (DLT) phase and an expansion phase (first-line patients). Primary objectives were safety/tolerability (DLT phase), and objective response rate (ORR) and duration of response (DOR) by modified RECIST (mRECIST) and RECIST version 1.1 (v1.1) per independent imaging review (IIR; expansion phase).
Results: A total of 104 patients were enrolled. No DLTs were reported (n = 6) in the DLT phase; 100 patients (expansion phase; included n = 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n = 29) or C disease (n = 71). At data cutoff, 37% of patients remained on treatment. Median duration of follow-up was 10.6 months (95% CI, 9.2 to 11.5 months). Confirmed ORRs by IIR were 46.0% (95% CI, 36.0% to 56.3%) per mRECIST and 36.0% (95% CI, 26.6% to 46.2%) per RECIST v1.1. Median DORs by IIR were 8.6 months (95% CI, 6.9 months to not estimable [NE]) per mRECIST and 12.6 months (95% CI, 6.9 months to NE) per RECIST v1.1. Median progression-free survival by IIR was 9.3 months per mRECIST and 8.6 months per RECIST v1.1. Median overall survival was 22 months. Grade ≥ 3 treatment-related adverse events occurred in 67% (grade 5, 3%) of patients. No new safety signals were identified.
Conclusion: Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.