Sintilimab in patients with advanced esophageal squamous cell carcinoma refractory to previous chemotherapy: A randomized, open-label phase II trial (ORIENT-2).
Abstract No : 4511
Abstract Type : Poster Discussion Session
Indication : Esophageal Carcinoma
Intervention : Sintilimab
Company : Innovent Biologics, Inc.
Technology : IgG4 Monoclonal antibody
From May 16, 2017 to Aug 30, 2018, 190 pts were randomly assigned to sintilimab or chemotherapy (n = 95 per group). With the median follow-up of 7.2 months for sintilimab group and 6.2 months for chemotherapy group, the median OS in sintilimab was significantly higher than chemotherapy (7.2m vs. 6.2m, hazard ratio [HR] 0.70, P = 0.034). The objective response rate (ORR) was greater in sintilimab than chemotherapy with 12.6% vs. 6.3%, and the median duration of response was longer (8.3m vs. 6.2m). Incidences of treatment-related adverse events (TRAEs) of any grade (54.3% vs. 90.8%) and of grade 3-5 (20.2% vs. 39.1%) were both numerically less in sintilimab than in chemotherapy. The ORR in sintilimab versus chemotherapy in pts with tumor PD-L1 tumor proportion score (TPS) $1% and with TPS $10% were 20.2% vs. 0%, and 35.7% vs. 0%, respectively. In sintilimab group, pts with low NLR ( , 3) had a significant longer median OS (HR 0.54, P = 0.019) than with high NLR.
Sintilimab was superior to chemotherapy with a significantly prolonged survival benefit and a favorable safety profile in pts with advanced ESCC refractory to first-line chemotherapy. High tumor PD-L1 expression (TPS $1% or $10%) might indicate more response benefit to sintilimab for these pts, and low NLR might be a positive predictive factor for sintilimab
Another PD-1 inhibitor (Sintilimab) jointly developed by Innovent and Eli Lilly has met its primary endpoint of overall survival in the second-line treatment of patients with metastatic esophageal squamous cell carcinoma (ORIENT-2 Study) and the company is planning to discuss these results with chinese regulatory authorities for immediate approval.
The phase 3 study (NCT03748134) comparing the Efficacy and Safety of Sintilimab vs. Placebo, in Combination With Chemotherapy, for First-Line Treatment of Unresectable, Locally Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma (ORIENT-15) is ongoing.