Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study

Lin Shen, Jun Guo, Qingyuan Zhang, Hongming Pan, Ying Yuan, Yuxian Bai, Tianshu Liu, Qing Zhou, Jun Zhao, Yongqian Shu, Xiaoming Huang, Siyang Wang, Jie Wang, Aiping Zhou, Dingwei Ye, Ting Sun, Yujuan Gao, Silu Yang, Zoubai Wang, Jian Li, Yi-Long Wu, Lin Shen, Jun Guo, Qingyuan Zhang, Hongming Pan, Ying Yuan, Yuxian Bai, Tianshu Liu, Qing Zhou, Jun Zhao, Yongqian Shu, Xiaoming Huang, Siyang Wang, Jie Wang, Aiping Zhou, Dingwei Ye, Ting Sun, Yujuan Gao, Silu Yang, Zoubai Wang, Jian Li, Yi-Long Wu

Abstract

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.

Keywords: oncology; tumours.

Conflict of interest statement

Competing interests: LS, JG, QZ, HP, YY, YB, TL, QZ, JZ, YS, XH, SW, JW, AZ, DY, TS, and Y-LW have nothing to declare. YG, SY, ZW, and JL are employees of BeiGene.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
(A) Overall survival (safety analysis set). (B) Progression-free survival (safety analysis set). OS, overall survival; PFS, progression-free survival.
Figure 2
Figure 2
Change of total sum of target lesion diameters from baseline abbreviations: dMMR, deficient mismatch repair; ESCC, esophageal squamous cell carcinoma; GC, gastric cancer; HCC, hepatocellular carcinoma; MSI-H; microsatellite instability-high; NPC, nasopharyngeal carcinoma; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; UC, urothelial bladder cancer.

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