Gls-010, a novel anti-PD-1 mAb in Chinese advanced gastrointestinal tumor: Result of a phase Ib clinical trial.

125 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Phase Ia exhibited good result of tolerance and 240mg fixed dose was selected. Phase Ib is to explore efficacy and biomarkers in different types of advanced cancer. Here we report the preliminary result in Chinese gastrointestinal (GI) tumor patients (pts) from the phase Ib. Methods: All pts enrolled received GLS-010 240mg every 2 weeks. Tumor response was assessed by RECIST 1.1 every 8 weeks. Adverse events (AEs) were graded by NCI CTCAE v4.03. Several biomarkers were evaluated, including PD-L1 by IHC, tissue tumor mutation burden (tTMB) by whole exome sequencing (WES) from FFPE tissue, blood TMB (bTMB) by the multi-gene panel based next-generation sequencing (NGS) from blood ctDNA. Results: Until September 2018, 23 pts (including 10 gastric cancer or GC, 10 esophagus cancer or EC, and 3 biliary tract cancer or BTC) were enrolled in the phase 1b. The median dosing number was 4 (range: 1~16). The most common treatment related AEs included haemoglobin decreased (16/23, G1-2), leukopenia (6/23, G1-2), fever (4/23, G1), blood bilirubin increased (4/23, G1-3), ALT increased (3/23, G1), etc. Treatment–related grade 3-5 AEs include 1 multiple organ dysfunction syndrome, 1 interstitial lung disease and 1 blood bilirubin increased. 21 pts received response evaluation. Four patients achieved partial response (PR), including 1 GC (1/9), 2 EC (2/10), and 1 BTC (1/2). 2 subjects had stable disease (SD) at Week 8, and were still in treatment. No apparent correlation was observed between treatment response and PD-L1 expression. However, both tTMB and bTMB data obtained from 18 patients support positive correlation to tumor response. The tTMB level of 3 PR pts with valid data is significantly higher than that of 9 PD pts (P = 0.036). The bTMB level of 4 PR pts with valid data is significantly higher than that of 10 PD pts (P = 0.049). Conclusions: GLS-010 showed promising efficacy and acceptable safety in Chinese patients. For Chinese GI tumor TMB may be a useful biomarker to predict the treatment response to PD-1 inhibitor. Comparing to tTMB, bTMB may be of more future value due to its applicability in clinical practice.