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

4519 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.