A Phase 1b Study of Lenvatinib plus Nivolumab in Patients with Unresectable Hepatocellular Carcinoma.

IF 10.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver Cancer Pub Date : 2026-01-09 DOI:10.1159/000549681

Masafumi Ikeda, Masatoshi Kudo, Kenta Motomura, Takuji Okusaka, Naoya Kato, Takashi Hisai, Hiroki Ikezawa, Sari Shiba, Taisuke Hoshi, Masataka Kuroda, Hiromitsu Kumada, Masahiro Kobayashi

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引用次数: 0

Abstract

Introduction: Despite recent advances in treatment for unresectable hepatocellular carcinoma (uHCC), median overall survival (OS) in the first-line setting across immune-based combination therapies has plateaued at 16-24 months. Evaluation of potentially more potent therapies is warranted. We report results of the first prospective phase 1b study of lenvatinib (multi-kinase inhibitor) + nivolumab (anti-programmed death receptor1 antibody) for treating advanced uHCC.

Methods: This open-label study was conducted in Japan among adults (≥20 years) with histologically/cytologically confirmed HCC. Patients received monotherapy-approved doses of either 8 mg (body weight <60 kg) or 12 mg (body weight ≥60 kg) oral lenvatinib once daily + 240 mg intravenous nivolumab every 2 weeks (days 1 and 15) in 4-week cycles. Part 1 planned to enroll 6 patients to evaluate the tolerability of lenvatinib+nivolumab. Part 2 evaluated safety and preliminary antitumor activity. Primary endpoints were dose-limiting toxicities (DLTs; part 1 only) and safety. Secondary endpoints were objective response rate (ORR) and pharmacokinetics of lenvatinib and nivolumab. Additional exploratory endpoints (including OS and progression-free survival [PFS]; part 2 only) were assessed.

Results: No DLT was observed among patients (n = 6) in part 1. Treatment-related adverse events (TRAEs) were observed in all patients (n = 30) in part 1 and 2. The most common TRAEs were palmar-plantar erythrodysesthesia syndrome (60%), dysphonia (53.3%), and decreased appetite (50.0%). Distributions of lenvatinib AUC_(0-t) were similar to those observed for lenvatinib in HCC previously and were within the distributions of AUC_(0-τ) observed with lenvatinib monotherapy in the REFLECT trial. ORR by mRECIST per investigator review was 66.7% in part 1 and 79.2% in part 2. In part 2, median PFS was 9.07 months by mRECIST per investigator review, and median OS was 26.94 months.

Conclusion: Lenvatinib+nivolumab was well tolerated and had encouraging antitumor activity in patients with advanced uHCC in this phase 1b study.

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Lenvatinib联合Nivolumab治疗不可切除肝细胞癌的1b期研究

导语：尽管最近在不可切除的肝细胞癌（uHCC）的治疗方面取得了进展，但一线免疫联合治疗的中位总生存期（OS）已稳定在16-24个月。评估潜在的更有效的治疗方法是必要的。我们报告lenvatinib（多激酶抑制剂）+ nivolumab（抗程序性死亡受体1抗体）治疗晚期uHCC的首个前瞻性1b期研究结果。方法：这项开放标签研究在日本进行，研究对象为组织学/细胞学证实HCC的成人（≥20岁）。结果：在第一部分中，未观察到患者（n = 6）接受单药批准剂量为8mg（体重）。在第1部分和第2部分中，观察到所有患者（n = 30）的治疗相关不良事件（TRAEs）。最常见的trae是掌跖红觉异常综合征（60%）、发音障碍（53.3%）和食欲下降（50.0%）。lenvatinib的AUC（0-t）分布与先前在HCC中观察到的lenvatinib相似，并且在REFLECT试验中lenvatinib单药治疗观察到的AUC（0-τ）分布范围内。在第一部分和第二部分中，mRECIST的每名研究者评价的ORR分别为66.7%和79.2%。在第2部分中，mRECIST每位研究者的中位PFS为9.07个月，中位OS为26.94个月。结论：在这项1b期研究中，Lenvatinib+nivolumab在晚期uHCC患者中具有良好的耐受性和令人鼓舞的抗肿瘤活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver Cancer Medicine-Oncology

CiteScore

20.80

自引率

7.20%

发文量

审稿时长

16 weeks

期刊介绍： Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.