The synergic combination of anti-PD-1/PD-L1 and antiangiogenic agents has exhibited as an encourage treatment pattern in aHCC. Multi-targeted antiangiogenic TKIs, such as lenvatinib and sorafenib, are approved for 1st-line treatment of aHCC. Sintilimab, a novel selective anti-PD-1 monoclonal antibody, has demonstrated encouraging clinical activities in aHCC. The trial aims to explore the safety and efficacy of sintilimab plus anlotinib (a TKI against angiogenesis) in aHCC.
This is a single-arm phase II study. Pts with aHCC, BCLC stage C or B (not amenable for surgery and chemoembolization), Child-Pugh scores≤7 and ECOG PS ≤ 1 received 1st-line treatment of sintilimab (200mg, iv, D1) plus anlotinib (12mg, po, QD, D1-14) every 3 wks until disease progression or unacceptable toxicity. Primary endpoints were safety and objective response rate (ORR, per RECIST 1.1), and secondary endpoints included disease control rate (DCR), progression free survival (PFS), duration of response (DOR) and overall survival (OS).
As of June 30, 2020, 16 pts with 14 males, median age 56 yrs (range 41-70), BCLC B /C (3/13), and Child-Pugh A/B7(15/1) were enrolled. All pts received at least two cycles of treatments with median cycles 7 (range 2-18). Median follow-up was 5.3 months (range 2.1-13.3). The most common treatment-related adverse events (TRAEs) were grade 1-2 with thrombocytopenia (50%), increased AST (37.5%), ALT (31.3%) and bilirubin (31.3%), decreased neutrophil count (31.3%), leukopenia (25%), hypertension (25%) and hand-foot syndrome (25%). 6 pts experienced manageable grade 3 TRAEs, and no grade 4/5. 7 pts required dose reduction of anlotinib (4 pts to 10 mg and 3 to 8 mg). No treatment withdraw caused by TRAEs. Of 14 evaluable pts, ORR was 42.9% (6/14) with 1 CR and 5 PR. 7 pts were SD, and DCR was 92.9% (13/14). Median DoR was not reached (95%CI: 9.0 months-not reached), and all the responses were ongoing at the data cutoff. 6m-PFS rate was 78.8% (95%CI: 38.1%-94.3%) and mPFS was unreached.
The combination of sintilimab and anlotinib showed promising clinical activities with manageable toxicity for first line treatment of aHCC. Enrolment is on-going to further validate the combination regimen.
NCT04052152.
Jiangsu Province Hospital - The First Affiliated Hospital with Nanjing Medical University.
Jiangsu province 333 high level Talents Project; Innovation Funds from Chinese Society of Clinical Oncology Youth Committee. Y-young2019-060; the Advanced Health Talent of Six-One Project of Jiangsu Province. LGY2017069; Joint Research Project by Southeast University and Nanjing Medical University. 3207027381; National Natural Science Foundation of China, 81472306; Key research and development program of Jiangsu Province.BE2016789.
All authors have declared no conflicts of interest.