Penpulimab (Anti-PD-1) combined with anlotinib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Updated results from a phase Ib/II study.

• DOI: 10.1200/jco.2021.39.3_suppl.306
• Publication Date: 2021-01-22T19:59:19Z
• Authors: Shun Chang Jiao; LI BAI; Jiahong Dong; Chunmei Bai; Chunhong Hu; Liangfang Shen; Qun Qin; Yuxian Bai; Jia Fan; Aimin Zang; Yanyun Zhu; Chun Han; Juan Li; Pengfei Zhang; Sisi Ye; Xindan Kang; Qian Qiao; Zhongmin Maxwell ...; Baiyong Li; Yu Xia
• Keywords: Clinical endpoint; Combination therapy

306 Background: Combined therapy of an immune checkpoint inhibitor with a targeted antiangiogenic agent had been proved to be effective for the treatment uHCC. Penpulimab was engineered eliminate FcγR binding and ADCC/ADCP completely, where effects could induce T-cell apoptosis clearance then compromise anti-tumor activity. demonstrated slower PD-1 antigen off-rate, which resulted in better cellular activity higher receptor occupancy. also showed numerous contacts N58 glycosylation on BC loop advantage facilitate interaction antibody might contribute off-rate. These structural differentiations offer more robust biological effect enhance penpulimab. Anlotinib is multi-targeted tyrosine kinase selective VEGF receptors 1/2/3, FGF 1-4, PDGF α β, c-kit. Methods: In this open-label, multicenter phase Ib/II study, patients (pts) without prior systemic treatment, classified as BCLC stage B (not amenable locoregional therapy) or C, Child-Pugh ≤7, ECOG PS ≤ 1 received (200mg IV Q3W) Anotinib (8 mg PO 2weeks on/1 week off). Primary endpoint ORR (RECIST v1.1); secondary endpoints were safety, DCR, DoR, TTP, PFS OS. Results: 31 pts (median age 56 years [23–74], 0/1 [64%/36%], B/C [23%/77%], HBV/HCV [61%/7%]) combined therapy. As August 31, 2020, median follow-up time 11.9 mons (range 3.7-17.7). Median 7.6 6-mons rate 57.6% while TTP 8.5 62.7%. overall survival not met OS 93.2%. The 31.0% (9/29) DCR 82.8% (24/29). At data cutoff, 77.8% responders remained ongoing still treatment. Treatment-related adverse events (TRAEs) occurred 90.3% (≥G3 16.1% [5/31], no G5, discontinuation 9.7% [3/31]). Most common TRAEs (≥15%) increased AST (38.7%) ALT (35.5%), blood bilirubin (22.6%),asthenia (22.6%),decreased platelet count (19.4%) rash (16.1%). Conclusions: plus favorable antitumor efficacy acceptable safety profile further randomized, 3 study combination at dose (10 2 weeks off) setting (NCT04344158).