Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study

作者：Jian-Ming Xu, Yun Zhang, Ru Jia, Chunyan Yue, Lianpeng Chang, Rongrui Liu, Gairong Zhang, Chuanhua Zhao, Yaoyue Zhang, Chunxia Chen, Yan Wang, Xin Yi, Zhiyuan Hu, Jianjun Zou, Quanren Wang · 发表于：Clinical Cancer Research · 年份：2018 · DOI：10.1158/1078-0432.ccr-18-2484 · 被引用次数：536 · 研究领域：Gastric Cancer Management and Outcomes、Hepatocellular Carcinoma Treatment and Prognosis、Esophageal Cancer Research and Treatment

PURPOSE: This study assessed the safety and efficacy of SHR-1210 (anti-PD-1 antibody) and apatinib (VEGFR2 inhibitor) as combination therapy in patients with advanced hepatocellular carcinoma (HCC), gastric, or esophagogastric junction cancer (GC/EGJC). PATIENTS AND METHODS: = 28) received apatinib at the phase Ia-identified recommended phase II dose (RP2D) plus SHR-1210. The primary objectives were safety and tolerability and RP2D determination. RESULTS: At data cutoff, 43 patients were enrolled. In phase Ia, four dose-limiting toxicity events were observed (26.7%): one grade 3 lipase elevation (6.7%) in the apatinib 250 mg cohort and three grade 3 pneumonitis events (20%) in the apatinib 500 mg cohort. The maximum tolerated RP2D for apatinib was 250 mg. Of the 33 patients treated with the R2PD combination, 20 (60.6%) experienced a grade ≥3 treatment-related adverse event; adverse events in ≥10% of patients were hypertension (15.2%) and increased aspartate aminotransferase (15.2%). The objective response rate in 39 evaluable patients was 30.8% (95% CI: 17.0%-47.6%). Eight of 16 evaluable HCC patients achieved a partial response (50.0%, 95% CI: 24.7%-75.4%). CONCLUSIONS: SHR-1210 and apatinib combination therapy demonstrated manageable toxicity in patients with HCC and GC/EGJC at recommended single-agent doses of both drugs. The RP2D for apatinib as combination therapy was 250 mg, which showed encouraging clinical activity in patients with advanced HCC.