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

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). Experimental Design: This was an open-label, dose-escalation (phase Ia) and expansion study (phase Ib). In phase Ia, patients (n=15) received SHR-1210 200 mg every 2 weeks and apatinib 125-500 mg once daily until unacceptable toxicity or disease progression. In phase Ib, patients (n=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 cut-off, 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 ORR 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 HCC and GC/EGJC patients 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.

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