Finn, Richard S.Ikeda, MasafumiZhu, Andrew X.Sung, Max W.Baron, Ari D.Kudo, MasatoshiOkusaka, TakujiKobayashi, MasahiroKumada, HiromitsuKaneko, ShuichiPracht, MarcMamontov, KonstantinMeyer, TimKubota, TomokiDutcus, Corina E.Saito, KenichiSiegel, Abby B.Dubrovsky, LeonidMody, KalgiLlovet i Bayer, Josep Maria2021-03-092021-03-092020-07-270936-6555https://hdl.handle.net/2445/174833PURPOSE 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 5 6) in the DLT phase; 100 patients (expansion phase; included n 5 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n 5 29) or C disease (n 5 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.20 p.application/pdfengcc-by-nc-nd (c) Finn et. al., 2020http://creativecommons.org/licenses/by-nc-nd/3.0/es/ImmunoglobulinesTumorsMedicamentsImmunoglobulinsTumorsDrugsinfo:eu-repo/semantics/article7061302021-03-09info:eu-repo/semantics/openAccess32716739