HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric adenocarcinoma: A phase II clinical trial.

Abstract

4524 Background: Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We investigated HX008, an Anti-PD1 Antibody, with irinotecan in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and/or fluoropyrimidine. Methods: This study is a multicenter, open, phase II clinical study of recombinant humanized anti-pd-1 monoclonal antibody HX008 injection plus Irinotecan that was conducted at 11 hospitals in China. Eligible patients are adults with histologically confirmed advanced gastric or gastro-oesophageal junction cancer. Subjects participating in this study are required to submit a archived tumor tissue specimen or newly obtained biopsy of tumor lesions at the site of no previous radiotherapy and peripheral blood (2mL) for detection of PD-L1 and MSI/MMR expression. The samples will be tested for expression of PD-L1 and MMR by immunohistochemistry (IHC) in the central laboratory, and MSI levels will be determined by polymerase chain reaction (PCR) and gel electrophoresis. Subjects received PD-1 monoclonal antibody HX008 at 200mg (d1, intravenous drip, once every 3 weeks) plus irinotecan at 160mg/m2 (d1, intravenous drip, 60 ~ 120min, once every 2 weeks). Response was assessed every 6 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Primary endpoints was objective remission rate (ORR). Results: Between October 2018 and September 2019, a total of 58 patients with advanced gastric or gastro-oesophageal junction cancer were enrolled in this study. Median (range) age was 61 (27-71) years, and most patients were male (72.4%). Among 53 patients who were evaluated, 15 (28.3%) experienced objective response and 22 (41.5%) experienced stable disease (SD). The median progression free survival (PFS) was 5.4 months, the one-year survival rate was 71.3%. The most common treatment-related adverse events of grade 3 or 4 included neutropenia(31.0%), anemia(15.5%), loss of appetite (6.9%), vomiting(5.2%), nausea(3.4%), diarrhea (1.7%) and fatigue (1.7%). There were no treatment-related deaths. Conclusions: HX008 injection plus Irinotecan demonstrated promising activity and manageable safety in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Clinical trial information: NCT03704246 .