Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203)

Chun Han, Sisi Ye, Chunhong Hu, Liangfang Shen, Qun Qin, Yuxian Bai, Shizhong Yang, Chunmei Bai, Aimin Zang, Shunchang Jiao, Li Bai, Chun Han, Sisi Ye, Chunhong Hu, Liangfang Shen, Qun Qin, Yuxian Bai, Shizhong Yang, Chunmei Bai, Aimin Zang, Shunchang Jiao, Li Bai

Abstract

Objective: This study aims to assess the efficacy and safety of penpulimab (a humanized anti-PD-1 IgG1 antibody) with anlotinib in the first-line treatment of Chinese patients with uHCC.

Methods: In this open-label multicenter phase Ib/II trial, patients with histologically or cytologically confirmed uHCC, without previous systemic treatment, aged 18-75 years old, classified as BCLC stage B (not amenable for locoregional therapy) or C, with Child-Pugh score ≤7 and ECOG performance status ≤1 were enrolled. Patients received penpulimab [200 mg intravenous (i.v.) Q3W] and oral anlotinib (8 mg/day, 2 weeks on/1 week off). The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), duration of response (DoR), and overall survival (OS). This trial is registered with ClinicalTrials.gov (NCT04172571).

Results: At the data cutoff (December 30, 2020), 31 eligible patients had been enrolled and treated with a median follow-up of 14.7 months (range, 1.4-22.1). The ORR was 31.0% (95% CI, 15.3-50.8%), and the DCR was 82.8% (95% CI, 64.2-94.2%). The median PFS and TTP for 31 patients were 8.8 months (95% CI, 4.0-12.3) and 8.8 months (95% CI, 4.0-12.9) respectively. The median OS was not reached; the 12-month OS rate was 69.0% (95% CI, 48.9-82.5%). Only 19.4% (6/31) of patients had grade 3/4 treatment-related adverse events (TRAEs).

Conclusion: Penpulimab plus anlotinib showed promising anti-tumor activity and a favorable safety profile as first-line treatment of patients with uHCC.

Keywords: anlotinib; antiangiogenics; first-line treatment; hepatocellular carcinoma; immune checkpoint inhibitors; penpulimab.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Han, Ye, Hu, Shen, Qin, Bai, Yang, Bai, Zang, Jiao and Bai.

Figures

Figure 1
Figure 1
Trial profile.
Figure 2
Figure 2
(A) Swimmer plot of patients who underwent at least two post-baseline tumor assessments; (B) Waterfall plot of best percentage change from baseline in sum of diameters with best overall response.
Figure 3
Figure 3
(A) Kaplan–Meier plot of progression-free survival (PFS); (B) Kaplan–Meier plot of time to progression (TTP); (C) Kaplan–Meier plot of overall survival (OS).

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