Статья

Phase ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma

R. Finn, M. Ikeda, A. Zhu, M. Sung, A. Baron, M. Kudo, T. Okusaka, M. Kobayashi, H. Kumada, S. Kaneko, M. Pracht, K. Mamontov, T. Meyer, T. Kubota, C. Dutcus, K. Saito, A. Siegel, L. Dubrovsky, K. Mody, J. Llovet,
2020

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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  • 1. Version of Record от 2020-09-10

Метаданные

Об авторах
  • R. Finn
    David Geffen School of Medicine at UCLA
  • M. Ikeda
    National Cancer Center Hospital East
  • A. Zhu
    Harvard Medical School, Fudan University Shanghai Cancer Center
  • M. Sung
    Tisch Cancer Institute
  • A. Baron
    California Pacific Medical Center
  • M. Kudo
    Kindai University School of Medicine
  • T. Okusaka
    National Cancer Center Hospital
  • M. Kobayashi
    Toranomon Hospital
  • H. Kumada
    Toranomon Hospital
  • S. Kaneko
    Kanazawa University
  • M. Pracht
    Centre Eugène Marquis Rennes
  • K. Mamontov
    Altai Regional Oncology Center
  • T. Meyer
    Royal Free London NHS Foundation Trust
  • T. Kubota
    Eisai Co., Ltd.
  • C. Dutcus
    Eisai Inc.
  • K. Saito
    Eisai Inc.
  • A. Siegel
    Merck &amp; Co., Inc.
  • L. Dubrovsky
    Merck &amp; Co., Inc.
  • K. Mody
    Eisai Inc.
  • J. Llovet
    Icahn School of Medicine at Mount Sinai, Universitat de Barcelona
Название журнала
  • Journal of Clinical Oncology
Том
  • 38
Выпуск
  • 26
Страницы
  • 2960-2970
Финансирующая организация
  • Merck Sharp and Dohme
Номер гранта
  • undefined
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC BY
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus