TY - JOUR T1 - Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2019-000437 VL - 8 IS - 1 SP - e000437 AU - Lin Shen AU - Jun Guo AU - Qingyuan Zhang AU - Hongming Pan AU - Ying Yuan AU - Yuxian Bai AU - Tianshu Liu AU - Qing Zhou AU - Jun Zhao AU - Yongqian Shu AU - Xiaoming Huang AU - Siyang Wang AU - Jie Wang AU - Aiping Zhou AU - Dingwei Ye AU - Ting Sun AU - Yujuan Gao AU - Silu Yang AU - Zuobai Wang AU - Jian Li AU - Yi-Long Wu Y1 - 2020/06/01 UR - http://jitc.bmj.com/content/8/1/e000437.abstract N2 - Background Tislelizumab is an investigational, humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death-1 (PD-1) that was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy.Methods The purpose of this phase 1/2, open-label, non-comparative study was to examine the safety, tolerability, and antitumor activity of tislelizumab in adult (≥18 years) Chinese patients with histologically or cytologically confirmed advanced solid tumors with measurable disease. The phase 1 portion of the study consisted of a dose-verification study and a pharmacokinetic (PK) substudy; phase 2 was an indication-expansion study including 11 solid tumor cohorts. Patients previously treated with therapies targeting PD-1 or its ligand, programmed cell death ligand-1 were excluded. During dose-verification, dose-limiting toxicities (DLTs) were monitored; safety and tolerability were examined and the previously determined recommended phase 2 dose (RP2D) was verified. The primary endpoint of phase 2 was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors V.1.1.Results As of December 1, 2018, 300 patients were treated with tislelizumab 200 mg intravenously once every 3 weeks (Q3W). Median duration of follow-up was 8.1 months (range 0.2–21.9). No DLTs were reported during the phase 1 dose-verification study and the RP2D was confirmed to be 200 mg intravenously Q3W. Most treatment-related adverse events (62%) were grade 1 or 2, with the most common being anemia (n=70; 23%) and increased aspartate aminotransferase (n=67; 22%). Of the 251 efficacy evaluable patients, 45 (18%) achieved a confirmed clinical response, including one patient from the PK substudy who achieved a complete response. Median duration of response was not reached for all except the nasopharyngeal carcinoma cohort (8.3 months). Antitumor responses were observed in multiple tumor types.Conclusions Tislelizumab was generally well tolerated among Chinese patients. Antitumor activity was observed in patients with multiple solid tumors.Trial registration number CTR20160872. ER -