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

person Huayan Xu Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Oncology，Peking University Cancer Hospital & Institute, Beijing, China info_outline Huayan Xu, Xinan Sheng, Li Zhou, Xieqiao Yan, Siming Li, Zhihong Chi, Chuanliang Cui, Lu Si, Bixia Tang, Lili Mao, BIN LIAN, Xuan Wang, Xue Bai, Juan Li, Jun Guo

Authors person Huayan Xu Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Oncology，Peking University Cancer Hospital & Institute, Beijing, China info_outline Huayan Xu, Xinan Sheng, Li Zhou, Xieqiao Yan, Siming Li, Zhihong Chi, Chuanliang Cui, Lu Si, Bixia Tang, Lili Mao, BIN LIAN, Xuan Wang, Xue Bai, Juan Li, Jun Guo Organizations Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Oncology，Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Beijing Cancer Hospital, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma Oncology, Beijing Cancer Hospital, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Oncology, Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology,Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma & Sarcoma,Peking University Cancer Hospital & Institute, Beijing, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). A phase II clinical study showed that RC48-ADC has a good effect on locally advanced or metastatic urothelial carcinoma with HER2-positive expression that failed standard chemotherapy. In the study, some patients with HER2-postive immunohistochemistry (IHC 2+) but negative FISH test still benefited from the treatment of RC48-ADC.This study was to evaluate the activity and safety of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. Methods: This study is an open-label, single-center, single-arm, phase II trial. Eligibility criteria include: histologically confirmed urothelial carcinoma, HER2-negasitive (IHC 0 or 1+), ECOG PS 0-1,and treated with ≥1 prior systemic treatment. Patients received RC48-ADC 2mg/kg q2w until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary objectives were activity (ORR) and safety. Second objectives included progress-free survival, disease control rate and overall survival. Results: As of February 2022(date cutoff),19 patients were enrolled. The median age was 64 years old(range:36-77). At baseline, there were 6 patients with HER2(IHC 0), and 13 patients with HER2(IHC 1+).Most patients (13/19) had visceral metastasis. 15(79%) patients had received≥2 lines treatment.At date cutoff, 19 patients were assessable for response. The objective response rate was 26.3% (95% CI:9.1%,51.2%) and the DCR was 94.7% (18/19). The mPFS was 5.5months (95% CI:3.9,6.8) and mOS was 16.4months (95% CI:7.1,21.7).All of the 6 patients with HER2(0) were SD in the study. The ORRs were 38% (5/13) in patients with HER2(IHC 1+),31% (4/13) in visceral metastasis,17% (1/6) in liver metastasis patients,27% (4/15) in patients post to ≥ 2 lines of treatment. Common treatment-related AEs were leukopenia (52.6%), hypoesthesia (47.4%),alopecia (47.4%), AST increase (42.1%), ALT increase (42.1%), and neutropenia (42.1%), fatigue (42.1%),nausea (26.3%), vomiting (15.8%).Most of these AEs were Grade 1 or 2. The AE of Grade 3 was neutropenia (10.5%). The SAE was CPK increased (5.3%). Conclusions: This study showed that RC48-ADC was safe and the ORR was 26.3% in HER-negative patients with locally advanced or metastatic urothelial carcinoma. The enrollment was completed and data will be updated later. Clinical trial information: NCT04073602.