DataSheet_1_Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Pha.docx (14.15 kB)
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DataSheet_1_Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study.docx

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posted on 31.05.2022, 05:32 authored by Xiaofeng Chen, Wei Li, Xiaofeng Wu, Fengjiao Zhao, Deqiang Wang, Hao Wu, Yanhong Gu, Xiao Li, Xiaofeng Qian, Jun Hu, Changxian Li, Yongxiang Xia, Jianhua Rao, Xinzheng Dai, Qianwen Shao, Jie Tang, Xiangcheng Li, Yongqian Shu
Purpose

Immune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 antibody sintilimab plus antiangiogenic TKI anlotinib for advanced HCC.

Methods and Materials

Pathologically-proven advanced HCC patients received sintilimab (200 mg) on day 1 and anlotinib (12 mg) once daily on days 1 to 14 every 3 weeks, with a safety run-in for the first six participants to assess dose-limiting toxicities (DLTs). The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1.

Results

Twenty advanced HCC patients were enrolled. No DLTs occurred in the safety run-in. All patients had treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 8 (40.0%) patients, the most common being decreased platelet count (10.0%) and increased γ-glutamyl transferase (10.0%). No grade 4/5 TRAEs occurred. Five (25%) patients developed immune-related AEs. The ORR was 35.0% (95%CI 15.4%-59.2%) per RECIST v1.1 and 55.0% (95%CI 31.5%-76.9%) per modified RECIST. At data cutoff (March 31, 2021), the median progression-free survival was 12.2 months (95%CI, 3.8 to not reached). The median PFS was significantly longer in patients with lower LDH levels (not reached [NR], 95% CI, 8.7 to NR vs. higher LDH levels 5.2 months, 95% CI 3.4 to NR; P=0.020) and a CONUT score ≤2 (NR, 95% CI 5.1 to NR vs. CONUT score >2 6.2 months, 95% CI 1.8 to NR; P=0.020). Furthermore, patients showing tumor response had a significantly higher median proportion of CD16+CD56+ NK cells than patients who had stable or progressive disease (21.6% vs. 14.6%; P=0.026).

Conclusion

Sintilimab plus anlotinib showed promising clinical activities with manageable toxicity as first-line treatment of advanced HCC.

History

References