Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study

Yuankai Shi; Xintian Qin; Xingchen Peng; Aiping Zeng; Jingao Li; Chuanben Chen; Sufang Qiu; Suming Pan; Yulong Zheng; Jing Cai; Xiaopin Chen; Shenhong Qu; Lizhu Lin; Jianli Huang; Hui Wu; Ying Lu; Wei Wang; Changlu Hu; Xia He; Zhonghua Yu; Xiaojian Liu; Bo Xie; Anwen Liu; Guangyuan Hu; Shanghua Jing; Qingyuan Zhang; Renhua Guo; Qi Li; Jinsheng Hong; Feng Jin; Juan Meng; Jianhua Shi; Peiguo Wang; Jiuwei Cui; Kunyu Yang; Xuebang Zhang; Xiaojiang Li; Liangfang Shen; Yuxiang He; Limin Zhai; Xiuhua Sun; Junyou Ge; Yan Qing; Dekang Zong

doi:10.1016/j.lanwpc.2022.100617

Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study

Lancet Reg Health West Pac. 2022 Oct 10:31:100617. doi: 10.1016/j.lanwpc.2022.100617. eCollection 2023 Feb.

Authors

Yuankai Shi¹, Xintian Qin², Xingchen Peng³, Aiping Zeng⁴, Jingao Li⁵, Chuanben Chen⁶, Sufang Qiu⁶, Suming Pan⁷, Yulong Zheng⁸, Jing Cai⁹, Xiaopin Chen¹⁰, Shenhong Qu¹¹, Lizhu Lin¹², Jianli Huang¹³, Hui Wu¹⁴, Ying Lu¹⁵, Wei Wang¹⁶, Changlu Hu¹⁷, Xia He¹⁸, Zhonghua Yu¹⁹, Xiaojian Liu²⁰, Bo Xie²¹, Anwen Liu²², Guangyuan Hu²³, Shanghua Jing²⁴, Qingyuan Zhang²⁵, Renhua Guo²⁶, Qi Li²⁷, Jinsheng Hong²⁸, Feng Jin²⁹, Juan Meng³⁰, Jianhua Shi³¹, Peiguo Wang³², Jiuwei Cui³³, Kunyu Yang³⁴, Xuebang Zhang³⁵, Xiaojiang Li³⁶, Liangfang Shen³⁷, Yuxiang He³⁷, Limin Zhai³⁸, Xiuhua Sun³⁹, Junyou Ge⁴⁰, Yan Qing⁴⁰, Dekang Zong⁴⁰

Affiliations

¹ Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center and National Clinical Research Center for Cancer and Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
² Department of Medical Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
³ Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
⁴ Department of Respiratory Oncology, Guangxi Cancer Prevention and Treatment Institution/ Guangxi Medical University Cancer Hospital, Nanning, China.
⁵ Department of Head and neck radiotherapy, Jiangxi Cancer Hospital, Nanchang, China.
⁶ Department of Oncology Radiotherapy, Fujian Cancer Hospital, Fuzhou, China.
⁷ Department of Oncology Radiotherapy, Yue Bei People's Hospital, Shaoguan, China.
⁸ Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁹ Department of Oncology Radiotherapy, Nantong Tumor Hospital, Nantong, China.
¹⁰ Department of Medical Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
¹¹ Department of Head and Neck Surgery, The people's hospital of Guangxi Zhuang Autonomous region, Nanning, China.
¹² Department of Medical Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
¹³ Department of Oncology Radiotherapy, Zhangzhou Municipal Hospital of Fujian Province/Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China.
¹⁴ Department of oncology radiotherapy, Henan Cancer Hospital, Zhengzhou, China.
¹⁵ Department of Medical Oncology, Liuzhou worker's Hospital, Liuzhou, China.
¹⁶ Department of Medical Oncology-Gastroenterology and Urology, Hunan Cancer Hospital, Changsha, China.
¹⁷ Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, China.
¹⁸ Department of Oncology Radiotherapy, Jiangsu Cancer Hospital, Nanjing, China.
¹⁹ Department of Medical Oncology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
²⁰ Department of Medical Oncology, Fudan University Cancer Hospital, Shanghai, China.
²¹ Department of Medical Oncology, General Hospital of Southern Theatre Command, Guangzhou, China.
²² Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
²³ Department of Medical Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
²⁴ Department of Otolaryngology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
²⁵ Department of Medical Breast Oncology, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, China.
²⁶ Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital, Nanjing, China.
²⁷ Department of Medical Oncology, Shanghai General Hospital, Shanghai, China.
²⁸ Department of Oncology Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
²⁹ Department of Head and Neck Oncology, The Affiliated Tumor Hospital of Guizhou Medical University, Guiyang, China.
³⁰ Department of Medical Oncology, Haikou People's Hospital, Haikou, China.
³¹ Department of Medical Oncology, Linyi Cancer Hospital, Linyi, China.
³² Department of Oncology Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
³³ Department of Medical Oncology, The First Hospital of Jilin University, Changchun, China.
³⁴ Department of Medical Oncology, Union Hospital, Tongji Medical College/Huazhong University of Science and Technology, Wuhan, China.
³⁵ Department of Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³⁶ Department of Head and Neck surgery, Yunnan Cancer Hospital, Kunming, China.
³⁷ Department of Medical Oncology, Xiangya Hospital Central South University, Changsha, China.
³⁸ Department of Head and Neck neoplasm, Shandong Cancer Hospital, Jinan, China.
³⁹ Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
⁴⁰ Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., Chengdu, China.

Abstract

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC).

Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologically confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1.

Findings: Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade ≥3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported.

Conclusion: In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167.

Funding: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015).

Keywords: Biomarker; Efficacy; KL-A167; Nasopharyngeal carcinoma; PD-L1; Safety.