Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma

Abstract

Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. This single-arm phase 2 trial (NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD-L1-positive urothelial carcinoma who progressed during/following platinum-containing therapy and had no prior PD-(L)1 inhibitor treatment. Patients were considered PD-L1 positive if ≥ 25% of tumor/immune cells expressed PD-L1 when using the VENTANA™ PD-L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow-up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy-evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression-free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment-related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3-4 treatment-related adverse events and occurred in ≥ 5% of patients. Three investigator-assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD-L1-positive urothelial carcinoma and had a manageable safety profile.

Keywords: Asian population; immunotherapy; programed death protein-1; tislelizumab; urothelial carcinoma.

Conflict of interest statement

Dingwei Ye, Jiyan Liu, Aiping Zhou, Qing Zou, Hanzhong Li, Cheng Fu, Hailong Hu, Jian Huang, Shaoxing Zhu, Jie Jin, Lulin Ma, Jianming Guo, Jun Xiao, Se Hoon Park, Dahong Zhang, and Feng Bi have nothing to disclose. Xiusong Qiu, Yuanyuan Bao, Lilin Zhang, and Wei Shen are employees of BeiGene, Ltd. The study was designed under the responsibility of BeiGene, Ltd, in conjunction with the steering committee. The study was funded, and tislelizumab was provided by, BeiGene Ltd. Additionally, BeiGene, Ltd. collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication.

© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Figures

FIGURE 1

Patient disposition

FIGURE 2

Best percent change in sum of target lesion diameters from baseline per independent review committee in efficacy‐evaluable patients with programmed death ligand 1‐positive urothelial carcinoma

FIGURE 3

Time and duration of confirmed responses per RECIST v1.1 by independent review committee. Gray bars represent the duration of response

FIGURE 4

Objective response rates (ORRs) per RECIST v1.1 by independent review committee by population subgroup. Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; IC, immune cell; PD‐L1, programmed death ligand 1; TC, tumor cell

FIGURE 5

Kaplan‐Meier plot of overall survival (OS) (safety analysis set). Abbreviation: CI, confidence interval

FIGURE 6

Kaplan‐Meier plot of PFS per RECIST version 1.1 by IRC (efficacy‐evaluable set). Abbreviations: CI, confidence interval; IRC, independent review committee; PFS, progression‐free survival; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1.