Recombinant humanized anti-PD-1 monoclonal antibody (JS001) as salvage treatment for advanced gastric adenocarcinoma: Preliminary results of an open-label, multi-cohort, phase Ib/II clinical study.

Abstract

108 Background: Patients with gastric adenocarcinoma (GC) or gastroesophageal junction cancer (GEC) often present with advanced or metastatic disease, which has poor prognosis and limited treatment options and represent an important unmet medical need especially in China/Asia. JS001, a humanized recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1 with its ligands PD-L1 and PD-L2, and promotes antigen specific T-cell activation. A phase I study of JS001 in Chinese patients with heavily pretreated solid tumors has demonstrated an acceptable safety profile in doses up to 10 mg/kg Q2W. Here we report the safety and efficacy of JS001 in a phase Ib/II clinical study in Chinese patients with refractory/metastatic GC. (Clinical trial ID: NCT02915432) Methods: Refractory/metastatic GC Patients receive JS001 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to the RECIST 1.1 criteria. Tumor PD-L1 expression as well as additional potential predictive biomarkers are monitored for correlation with clinical response. Results: Between Apr 19, 2017 and Sep 11, 2017, 48 GC pts (74.5% received at least 2 Lines of treatment) were enrolled into the study. Treatment related adverse events occurred were mostly grade 1 or 2. As of Sep 11, 2017, 25 GC pts have been evaluated for clinical efficacy. 5 PR (partial response) and 10 SD (stable disease) were observed (ORR 20% and DCR 60%). The PD-L1 expression positivity (defined as positive staining ³1% on Tumor Cell or on Immune Cell by SP142) in EC tumor was 14.3% (7/48). 3/5 (60%) PD-L1+ patients and 2/20 (10%) PD-L1 negative patients achieved partial responses. Conclusions: JS001 showed a promising preliminary clinical activity in heavily pre-treated metastatic GC pts with a manageable safety profile. Of the 25 evaluable GC patients by 9/11/2017, 5 PR and 10 SD were observed (ORR 20% and DCR 60%). Among PD-L1 positive patients (n=5), ORR was 60% and DCR 80%. Pts will be continuously monitored for safety and efficacy upon JS001 treatment. Clinical trial information: NCT02915432.