The combination of immune checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) manifested high efficacy in uHCC. Anlotinib was a novel oral multi-targeted TKI selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Penpulimab, a humanized anti-PD-1 IgG1 monoclonal antibody, was engineered to eliminate FcγR binding, consequently eliminating ADCC, ADCP and ADCR effects. This AK105-203 trial (NCT04172571) aimed to explore the efficacy and safety of penpulimab plus anlotinib in patients (pts) with histologically or cytologically confirmed uHCC.
In this single-arm, multicenter phase Ib/II trial, pts with uHCC and no prior systemic treatment were eligible if they were 18-75 years, and classified as BCLC stage B (not amenable for locoregional therapy) or C, Child-Pugh score ≤7 and ECOG PS of 0-1. Pts received anlotinib (8 mg, p.o., qd, d1-14, q3w) plus penpulimab (200mg, iv, d1, q3w). The primary endpoint was ORR (RECIST v1.1). Secondary endpoints were safety, DCR, DoR, TTP, PFS and OS.
31 pts (median age 56 years [23-74], ECOG 0/1 [64%/36%], BCLC B/C [23%/77%], HBV/HCV [61%/7%]) received combined therapy. As of August 5, 2022, median follow-up time was 23.0 months (range 3.7-31.9). The ORR was 31.0% (95% CI, 15.3-50.8%), and 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, 4.0-14) respectively. OS events were observed in 16 patients (51.6%), and the median OS was 23.0 months with 12-months OS rate was 67.9%. Treatment-related adverse events (TRAEs) occurred in 90.3% of pts (≥G3 in 25.8% [8/31]). No G5 AE occurred. Most common TRAEs (≥25%) were increased AST (41.9%) and ALT (35.5%), general disorders and administration site conditions (35.5%), skin and subcutaneous tissue disorders (32.3%), platelet count decreased (25.8%), asthenia (25.8%).
Anlotinib combined with penpulimab showed encouraging efficacy and acceptable safety in pts with uHCC. The further randomized, phase 3 study of penpulimab plus anlotinib at a higher dose (10 mg) in this setting is ongoing (NCT04344158).
NCT04172571, release date November 21, 2019.
Akeso, Inc.
Akeso, Inc.
All authors have declared no conflicts of interest.