Supplementary Material for: A Phase 1b Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116

Background: Treatment with lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh <60 kg, the dose was 8 mg/day) plus pembrolizumab 200 mg once every 3 weeks demonstrated antitumor activity and a manageable safety profile in patients with first-line unresectable hepatocellular carcinoma (uHCC) in the open-label phase 1b Study 116/KEYNOTE-524 (primary analysis data cutoff date: October 31, 2019; median follow-up: 10.6 months).
Objective: This analysis (updated data cutoff date: March 31, 2021) reports efficacy results from 17 months of additional follow-up time.
Methods: 100 Patients with uHCC were included in the primary analysis (median follow-up: 27.6 months). Endpoints included overall survival (OS) and investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per modified RECIST. Landmark analyses of OS by best response at 3 and 9 months were performed. Pembrolizumab antidrug antibodies (ADAs) and concentrations were also measured (cutoff date: August 7, 2020).
Results: ORR was 43.0% (95% CI 33.1% to 53.3%) and median DOR was 17.1 months (95% CI 6.9 to 19.3 months). Median PFS and OS were 9.3 months (95% CI 7.4 to 9.8 months) and 20.4 months (95% CI 14.4 to 25.9 months), respectively. No treatment-emergent ADAs were detected.
Conclusion: Results show a sustained treatment effect with lenvatinib plus pembrolizumab in patients with uHCC in the first-line setting.

背景：针对一线不可切除肝细胞癌（unresectable hepatocellular carcinoma, uHCC）患者，乐伐替尼（lenvatinib，体重≥60kg者给药剂量为12mg/日，体重<60kg者为8mg/日）联合每3周一次的200mg帕博利珠单抗（pembrolizumab），在开放标签1b期研究116/KEYNOTE-524中展现出抗肿瘤活性与可管理的安全性特征（初始分析数据截止日期：2019年10月31日；中位随访时间：10.6个月）。
研究目的：本次分析（更新后数据截止日期：2021年3月31日）报告了额外17个月随访周期后的疗效结果。
研究方法：初始分析共纳入100例uHCC患者，中位随访时间为27.6个月。研究终点包括总生存期（overall survival, OS）、研究者评估的无进展生存期（progression-free survival, PFS）、客观缓解率（objective response rate, ORR）以及基于改良实体瘤疗效评价标准（modified RECIST）的缓解持续时间（duration of response, DOR）。此外还开展了3个月和9个月时基于最佳疗效的OS里程碑分析，并于2020年8月7日的数据截止节点检测了帕博利珠单抗的抗药物抗体（antidrug antibodies, ADAs）及药物浓度。
研究结果：客观缓解率为43.0%（95%置信区间33.1%~53.3%），中位缓解持续时间为17.1个月（95%置信区间6.9~19.3个月）；中位无进展生存期与总生存期分别为9.3个月（95%置信区间7.4~9.8个月）与20.4个月（95%置信区间14.4~25.9个月）。未检测到治疗诱导出现的抗药物抗体。
研究结论：结果显示，乐伐替尼联合帕博利珠单抗用于一线不可切除肝细胞癌患者时，可带来持续的治疗获益。