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
Authors: Shen Lin , Gong Jifang , Song Yuqin , Ye Dingwei , Lu Zhihao , Wang Siyang , Peng Peijian , Chen Jianhua , Jiang Ou , Zhang Guojun , Bai Yuxian , Pan Jianji , Ma Chunguang , Chen Li , Ba Yi , Li Qi , Lu Ping , Zhang Lingli , Yin Xianli , Gu Shanzhi , Zhang Huilai , Su Hang , Jiang Yongsheng , Cao Bangwei , Han Weiqing , Sun Yan , Zhang Feng , Ouyang Weiwei , Dong Haiying , Guo Jianming , Guo Yabing , Xu Chongyuan , Qi Junyuan , Wang Li , Lv Jun , Wang Xiang , Chen Chris , Li Jing , Zheng Yong , Jin Ge , Yang Yining , Zhao Guodong , Yang Fan , Xu Kehui , Liang Xiangying , Pan Zhaoyang , Meng Haijin 
Published: September 2020

Abstract
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 (&gt;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 preliminarily demonstrated that tTMB may be valuable biomarkers to predict the treatment response and benefit of GLS-010. For Chinese EC pts, tTMB and bTMB may be of value in predicting the response to PD-1 inhibitor.
Citation Format: Lin Shen, Jifang Gong, Yuqin Song, Dingwei Ye, Zhihao Lu, Siyang Wang, Peijian Peng, Jianhua Chen, Ou Jiang, Guojun Zhang, Yuxian Bai, Jianji Pan, Chunguang Ma, Li Chen, Yi Ba, Qi Li, Ping Lu, Lingli Zhang, Xianli Yin, Shanzhi Gu, Huilai Zhang, Hang Su, Yongsheng Jiang, Bangwei Cao, Weiqing Han, Yan Sun, Feng Zhang, Weiwei Ouyang, Haiying Dong, Jianming Guo, Yabing Guo, Chongyuan Xu, Junyuan Qi, Li Wang, Jun Lv, Xiang Wang, Chris Chen, Jing Li, Yong Zheng, Ge Jin, Yining Yang, Guodong Zhao, Fan Yang, Kehui Xu, Xiangying Liang, Zhaoyang Pan, Haijin Meng. GLS-010, a novel fully human anti-PD-1 mAb in patients with advanced tumor: Preliminary results of a Phase Ib clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3275.