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Cited by 1,167Hepatocellular Carcinoma Treatment and PrognosisCancer Immunotherapy and BiomarkersColorectal Cancer Treatments and Studies

Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma

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Finn, Richard S., Ikeda, Masafumi, Zhu, Andrew X., Sung, Max W., Baron, Ari D., Kudo, Masatoshi, Okusaka, Takuji, Kobayashi, Masahiro +12 more·2020·Journal of Clinical Oncology
DOI 10.1200/jco.20.00808PMC PMC7479760
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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.

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Research works printed but not linked: 24

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Authors
Finn, R. S., Ikeda, M., Zhu, A. X., Sung, M. W., Baron, A. D., Kudo, M., Okusaka, T., Kobayashi, M., Kumada, H., Kaneko, S., Pracht, M., Mamontov, K., Meyer, T., Kubota, T., Dutcus, C. E., Saito, K., Siegel, A. B., Dubrovsky, L., Mody, K., & Llovet, J. M.
Affiliations
  • University of California, Los Angeles (US)
  • National Cancer Center Hospital East (JP)
  • Harvard University (US)
  • Tisch Cancer Institute (US)
  • Sutter Health (US)
  • Kindai University Hospital (JP)
  • National Cancer Center Hospital (JP)
  • Toranomon Hospital (JP)
  • Kanazawa University (JP)
  • Centre Eugène Marquis (FR)
  • Altay Regional Oncological Hospital, Barnaul, Russian Federation
  • National Health Service (GB)
  • Eisai (Japan) (JP)
  • Eisai (United States) (US)
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
  • Hospital Clínic de Barcelona (ES)
Corresponding author
Llovet, Josep M.
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2020-09-10
Volume
38
Issue
26
Pages
2960-2970
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.20.00808
PMC
PMC7479760
OpenAlex
W3045387409
Cited by
1,167
References
2
Citations by year
2026: 67 · 2025: 132 · 2024: 197 · 2023: 257 · 2022: 262 · 2021: 197 · 2020: 42 · 2019: 8 · 2018: 2
FWCI
111.73
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Cancer Research UK (26813)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
lenvatinib, pembrolizumab, hepatocellular carcinoma, unresectable liver cancer, PD-1 inhibitors, multikinase inhibitor, combination immunotherapy, tumor microenvironment, objective response rate, duration of response, progression-free survival, dose-limiting toxicity, first-line therapy, immune-related adverse events, predictive biomarkers
MeSH terms
Progression-Free Survival, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Neoplasm Staging, Phenylurea Compounds, Quinolines, Time Factors, Disease Progression, Antibodies, Monoclonal, Humanized

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