A phase II study of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma.

Xinan Sheng Peking University Cancer Hospital, Beijing, China info_outline Xinan Sheng, Ai-Ping Zhou, Xin Yao, Yanxia Shi, Hong Luo, Benkang Shi, Jiyan Liu, Guohua Yu, Zhisong He, Changlu Hu, Weiqing Han, Jianmin Fang, Jun Guo

Authors Xinan Sheng Peking University Cancer Hospital, Beijing, China info_outline Xinan Sheng, Ai-Ping Zhou, Xin Yao, Yanxia Shi, Hong Luo, Benkang Shi, Jiyan Liu, Guohua Yu, Zhisong He, Changlu Hu, Weiqing Han, Jianmin Fang, Jun Guo Organizations Peking University Cancer Hospital, Beijing, China, National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Tianjin Cancer Hospital, Tianjin, China, Sun Yat-Sen university Cancer Center, Guangzhou, China, Chongqing Cancer Hospital, Chongqing, China, Qilu Hospital of Shandong University, Jinan, China, West China Hospital, Sichuan University, Chengdu, China, Weifang People′s Hospital, Weifang, China, Peking University First Hospital, Beijing, China, Anhui Provincial Cancer Hospital, Hefei, China, Hunan Cancer Hospital, Changsha, China, School of Life Science and Technology, Tongji University, Shanghai, China, Peking University Cancer Hospital and Institute, Beijing Shi, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Urothelial carcinoma (UC) is the third largest cancer type with HER2 positive cancer. RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). This study was to evaluate the activity of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma (mUC). Methods: This study is an open-label, multicenter, single-arm, non-randomized phase II study. Eligibility criteria include: histologically confirmed UC, HER2-positive (IHC 2+ or 3+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2 mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary endpoint was objective response rate (ORR). Progress-free survival (PFS), overall survival (OS), and safety was also assessed. Results: Patient enrollment for this study was completed in November 2018. A total of 43 patients were enrolled, with a median age of 64 years old. At baseline, most patients (37/43) had visceral metastasis. Fourteen (32.6%) patients had received ≥ 2 lines treatment and 8 (18.6%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 60.5% (95% CI: 44.4%, 75.0%) and the DCR was 90.7% (39/43). As of Jan 23, 2019, the median PFS for the overall study population was not yet reached, and the median PFS was 7.8 months (95% CI: 4.9, 10.7) for the 9 patients who started RC48-ADC prior to Jun 30, 2018. The ORR was 70.6% (12/17) in patients with HER2 FISH+ or IHC3+. The ORR was 64.9% (24/37) in patients with visceral metastasis and was 70.0% (14/20) in liver metastasis patients especially. The ORR was 64.3% in patients post to ≥ 2 lines treatment and 75.0% in patients post to immunotherapy. Common treatment-related AEs were leukopenia (51.2%), hypoesthesia (41.9%), alopecia (41.9%), neutropenia (37.2%), fatigue (34.9%), ALT increase (32.6%), and AST increase (32.6%); Most were Grade 1 or 2. Conclusions: RC48-ADC has demonstrated a clinically meaningful ORR of 60.5% in pretreated HER-2 positive mUC patients including those who underwent failure to the immunotherapy. Clinical trial information: NCT03507166