Abstract 3275: GLS-010, a novel fully human anti-PD-1 mAb in patients with advanced tumor: Preliminary results of a Phase Ib clinical trial

Background: GLS-010 is a novel fully human anti-PD-1 mAb developed by the OMT transgenic rat platform. In Phase 1a study, GLS-010 exhibited good tolerance and 240mg (Q2W) was selected. Phase 1b study was conducted to evaluate the safety,anti-tumor activity and explore biomarkers of GLS-010 in pts with advanced solid tumors or lymphomas. Methods: All pts enrolled received GLS-010 240 mg 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 explored, including PD-L1 by SP263 assay, tissue tumor mutation burden (tTMB) by whole exome sequencing (WES) from FFPE tissue, blood TMB (bTMB) by multi-gene panel based next-generation sequencing (NGS) from blood ctDNA. Results: As of 19 JUL 2019, 213 pts, median age of 55 (range: 21-75) years, were enrolled and 109 of 213 pts were still in treatment. The median dosing number was 7.5 (range: 1~41). Treatment-related AEs (TRAEs) occurred in 185 patients (70%), of which mostly were CTCAE grade 1-2. The most frequent TRAEs were related to hepatotoxicity, included “ALT increased” (32/213), “AST increased” (32/213), “blood bilirubin increased” (25/213). 53 of 163 pts, who received ≥1 response evaluation, achieved response (PR+CR, unconfirmed response included), including GC (4/21), EC (5/25), BTC (3/10), NSCLC (8/32), nasopharynx cancer (10/26),UC (2/8), HCC (0/12), cHL (18/21) and peripheral T/NK cell lymphoma (3/8). In all solid tumor types, pts with PD-L1-positive tumors experienced clinical benefit with significantly higher ORR (39.6% vs 14.5%, p=0.0025) and longer PFS (p=0.0241). ORR was higher for PD-L1 positive (TC≥25%) pts with lung cancer (66.7% vs 20.0%, p=0.051). For pan-caner analysis, ORR benefits of GLS-010 were also enhanced (51.9% versus 26.4%, p=0.0298) in pts with tTMB-high (>75th percentile, of each tumor type) versus tTMB-low. Pairing tTMB and survival data were analyzed in 129 pts, and tTMB-high pts benefit more with a significantly improved PFS (p=0.011). Also, improved PFS was observed in tTMB-high pts with EC (p=0.0059). For bTMB-high group, pts with EC achieved higher ORR (42.9% vs 6.3%, p=0.0672), which translated into PFS benefits (p=0.03). Conclusion: In conclusion, it is suggested that GLS-010 was well tolerated and had durable antitumor activity in Chinese tumor pts. PD-L1 has showed to be predictive of GLS-010 activity in solid tumors, especially in lung cancer. For pan-cancer analysis, it is prelimin