Safety, Efficacy, and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03.

Abstract

PURPOSE:

Immunotherapy offers a second-line option for patients with metastatic urothelial carcinoma (mUC) who failed standard therapy, but the biomarkers for predicting response remain to be explored. This study aims to evaluate the safety, efficacy, and correlative biomarker of toripalimab in patients with previously treated mUC.

PATIENTS AND METHODS:

Patients with mUC received toripalimab 3 mg/kg Q2W. Clinical response was assessed every 8 weeks by an independent review committee per RECIST v1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated.

RESULTS:

Among the intention-to-treat population (n = 151), 85% of the patients experienced treatment-related adverse event (TRAE) and 20% experienced grade 3 and above TRAE. The objective response rate (ORR) was 26% with a disease control rate (DCR) of 45%. The median duration of response, progression-free survival (PFS), and overall survival (OS) were 19.7 months [95% confidence interval (CI): 13.9-not estimable], 2.3 months (95% CI, 1.8-3.6), and 14.4 months (95% CI, 9.3-23.1), respectively. Both PD-L1+ and TMB-high (10 mutations/Mb as the cutoff) patients had better ORR than PD-L1- patients (42% vs. 17%, P = 0.002) and TMB-low patients (48% vs. 22%, P = 0.014), respectively. The TMB-high group also showed better PFS (12.9 vs. 1.8 months, P < 0.001) and OS (not reached versus 10.0 months, P = 0.018) than the TMB-low group.

CONCLUSIONS:

Toripalimab has demonstrated encouraging clinical activity in the second-line treatment of mUC with a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.

• Authors: Xinan Sheng, Haige Chen, Bin Hu, Xudong Yao, Ziling Liu, Xin Yao, Hongqian Guo, Yi Hu, Zhigang Ji, Hong Luo, Benkang Shi, Jiyan Liu, Jin Wu, FangJian Zhou, Zhisong He, Jinhai Fan, Weifeng Wang, Hui Feng, Sheng Yao, Patricia Keegan, Yiran Huang, Jun Guo
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 3 Pg. 489-497 (02 01 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 34740921 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• toripalimab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (therapeutic use)
• B7-H1 Antigen (genetics, metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Transitional Cell (diagnosis, drug therapy)
• Female
• Gene Expression
• Humans
• Male
• Middle Aged
• Safety
• Treatment Outcome
• Urinary Bladder Neoplasms (diagnosis, drug therapy)