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Efficacy and Safety of RC48-ADC, a Her2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma: A Phase 2, Open-Label, Multi-Centre, Single-Arm Study

118 Pages Posted: 2 Oct 2019

See all articles by Xinan Sheng

Xinan Sheng

Peking University - Key Laboratory of Carcinogenesis and Translational Research

Xieqiao Yan

Peking University - Key Laboratory of Carcinogenesis and Translational Research

Lin Wang

Chinese Academy of Medical Sciences - State Key Lab of Molecular Oncology

Yanxia Shi

Sun Yat-sen University (SYSU) - Department of Medical Oncology

Xin Yao

Tianjin Medical University

Hong Luo

Chongqing University

Benkang Shi

Shandong University - Qilu Hospital

Jiyan Liu

Sichuan University - Department of Medical Oncology

Zhisong He

Peking University - Department of Urology

Guohua Yu

Government of the People's Republic of China - Weifang No. 2 People's Hospital

Jianming Ying

Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) - Department of Pathology

Weiqing Han

Central South University - Affiliated Cancer Hospital

Changlu Hu

Anhui Provincial Cancer Hospital

Yun Ling

Chinese Academy of Medical Sciences - National Cancer Center

Zhihong Chi

Peking University - Key Laboratory of Carcinogenesis and Translational Research

Chuanliang Cui

Peking University - Key Laboratory of Carcinogenesis and Translational Research

Lu Si

Peking University - Key Laboratory of Carcinogenesis and Translational Research

Jianmin Fang

RemeGen, Ltd.

Aiping Zhou

Chinese Academy of Medical Sciences - State Key Lab of Molecular Oncology

Jun Guo

Peking University - Key Laboratory of Carcinogenesis and Translational Research

More...

Abstract

Background: Platinum-containing chemotherapy is the standard first-line treatment of advanced urothelial carcinoma (UC). After the failure of the first-line treatment, emerging anti-PD-1/L1 therapies yield rather low response rates. RC48-ADC is a novel HER2-targeting antibody-drug conjugate (ADC). We aimed to evaluate the efficacy and safety of RC48-ADC in patients with HER2-positive locally advanced or metastatic UC.

Methods: This is a phase 2, open-label, multi-centre, single-arm study of RC48-ADC at 2·0 mg/kg intravenously once every two weeks in patients with HER2-positive (immunohistochemical status 3+ or 2+ by central lab) locally advanced or metastatic UC who had failed with at least one line systemic chemotherapy. The primary endpoint was objective response rate (ORR) assessed by blinded independent review committee (BIRC)- per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1·1. The secondary endpoint included progression-free survival, duration of response, disease control rate, overall survival and safety.

Findings: From 28 December 2017 to 28 November 2018, 43 patients were enrolled and treated with RC48-ADC. The median follow-up was 11·8 months. The confirmed ORR as assessed by BIRC was 51·2% (95% CI: 35·5%, 66·7%). Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti-PD-1/L1 therapies. Median progression-free survival was 6·9 months (95% CI: 5·3, 8·3). Median overall survival was 13·9 months (95% CI: 9·0, NE). The most commonly treatment-related adverse events (TRAEs) were hypoaesthesia (60·5%), alopecia (55·.8%), and leukopenia (55·8%). No Grade 4 or Grade 5 TRAE had occurred. Twenty-four (55·8%) patients experienced Grade 3 TRAEs, including hypoaesthesia (18·6%) and neutropenia (14·0%). Interpretation RC48-ADC manifested clinically meaningful efficacy and a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC who were previously treated with platinum-containing chemotherapy and/or anti-PD-1/L1 therapies.

Clinical Trial Registration: This study is registered with ClinicalTrials.gov, number NCT03507166.

Funding Statement: RemeGen, Ltd., funded the study and provided the study drug. This work was also supported by grants from Natural Science Foundation of China (81672696) and Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20181101).

Declaration of Interests: JG is the member of the advisory board/consultant of MSD, Roche, Pfizer, Bayer, Novartis, Simcere, Shanghai Junshi Bioscience, Oriengene. JF are employees and shareholders of RemeGen, Ltd. All the other authors declare no conflict of interest.

Ethical Approval Statement: All the patients provided written informed consent before joining the study. The study protocol was approved by a relevant institutional review board or ethics committee of each study centre. The study was compliant with the Declaration of Helsinki and Good Clinical Practice guidelines.

Suggested Citation

Sheng, Xinan and Yan, Xieqiao and Wang, Lin and Shi, Yanxia and Yao, Xin and Luo, Hong and Shi, Benkang and Liu, Jiyan and He, Zhisong and Yu, Guohua and Ying, Jianming and Han, Weiqing and Hu, Changlu and Ling, Yun and Chi, Zhihong and Cui, Chuanliang and Si, Lu and Fang, Jianmin and Zhou, Aiping and Guo, Jun, Efficacy and Safety of RC48-ADC, a Her2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma: A Phase 2, Open-Label, Multi-Centre, Single-Arm Study (September 27, 2019). Available at SSRN: https://ssrn.com/abstract=3460675 or http://dx.doi.org/10.2139/ssrn.3460675

Xinan Sheng

Peking University - Key Laboratory of Carcinogenesis and Translational Research

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Xieqiao Yan

Peking University - Key Laboratory of Carcinogenesis and Translational Research

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Lin Wang

Chinese Academy of Medical Sciences - State Key Lab of Molecular Oncology

Beijing, 100021
China

Yanxia Shi

Sun Yat-sen University (SYSU) - Department of Medical Oncology

651 Dongfeng Road East
Guangzhou, 510060
China

Xin Yao

Tianjin Medical University

Tianjin, 300060
China

Hong Luo

Chongqing University

Shazheng Str 174, Shapingba District
Chongqing 400044, Chongqing 400030
China

Benkang Shi

Shandong University - Qilu Hospital

Jinan
China

Jiyan Liu

Sichuan University - Department of Medical Oncology

No 37, Guoxue Road
Wuhou District
Chengdu, 610041
China

Zhisong He

Peking University - Department of Urology

China

Guohua Yu

Government of the People's Republic of China - Weifang No. 2 People's Hospital

151 Guangwen St, Kuiwen Qu
Weifang Shi, 261000
China

Jianming Ying

Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) - Department of Pathology

Panjiayuan 17#, Chaoyang District, Beijing, 100021
Beijing, 100021
China

Weiqing Han

Central South University - Affiliated Cancer Hospital

Changsha
China

Changlu Hu

Anhui Provincial Cancer Hospital

Hefei
China

Yun Ling

Chinese Academy of Medical Sciences - National Cancer Center

Beijing
China

Zhihong Chi

Peking University - Key Laboratory of Carcinogenesis and Translational Research

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Chuanliang Cui

Peking University - Key Laboratory of Carcinogenesis and Translational Research

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Lu Si

Peking University - Key Laboratory of Carcinogenesis and Translational Research

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Jianmin Fang

RemeGen, Ltd.

China

Aiping Zhou

Chinese Academy of Medical Sciences - State Key Lab of Molecular Oncology

Beijing, 100021
China

Jun Guo (Contact Author)

Peking University - Key Laboratory of Carcinogenesis and Translational Research ( email )

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

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