Journal Article

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

Liu, Jiyan, Huang, Jian, Bi, Feng, Hu, Hailong, Ye, Dingwei, Bao, Yuanyuan, Zhang, Lilin, Zou, Qing, Park, Se Hoon, Li, Hanzhong, Xiao, Jun, Jin, Jie, Fu, Cheng, Shen, Wei, Zhu, Shaoxing, Ma, Lulin, Zhang, Dahong, Qiu, Xiusong, Guo, Jianming, Zhou, Aiping

2021

Overview

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. Tislelizumab is a unique anti‐PD‐1 antibody that was engineered specifically to minimize FcγR binding in order to limit antibody‐dependent phagocytosis, a potential mechanism of resistance to anti‐PD‐1 therapy. In the current study, tislelizumab demonstrated clinically meaningful antitumor activity in patients with previously treated locally advanced or metastatic PD‐L1‐positive urothelial carcinoma and had a manageable safety profile with no new safety signals compared with other anti‐PD‐L1/PD‐1 therapies. A phase 3 study of tislelizumab as treatment for urothelial carcinoma (NCT03967977) is currently ongoing and is recruiting patients.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adult / Adverse events / Aged / Aged, 80 and over / Anemia / Antibodies / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Agents, Immunological - therapeutic use / Apoptosis / Asian Continental Ancestry Group / Asian population / Biomarkers / Bladder / Cancer therapies / Carcinoma, Transitional Cell - drug therapy / Carcinoma, Transitional Cell - mortality / Chemotherapy / Clinical Research / Consent / Demographics / Female / Fever / Humans / Hyponatremia / Immune clearance / immunotherapy / Ligands / Lymphatic system / Macrophages / Male / Metastases / Metastasis / Middle Aged / Monoclonal antibodies / Neoplasm Recurrence, Local - drug therapy / Neoplasm Recurrence, Local - mortality / Original / Patients / PD-L1 protein / Phagocytosis / Platinum / programed death protein‐1 / Progression-Free Survival / Targeted cancer therapy / tislelizumab / Tumors / Urologic Neoplasms - drug therapy / Urologic Neoplasms - mortality / Urothelial carcinoma