Abstract 80P
Background
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.
Methods
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.
Results
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%).
Conclusions
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).
Clinical trial identification
NCT04172571, release date November 21, 2019.
Legal entity responsible for the study
Akeso, Inc.
Funding
Akeso, Inc.
Disclosure
All authors have declared no conflicts of interest.