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

Abstract

e17113 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 benefit from the treatment of RC48-ADC.The 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, one-arm, non-randomized phase II trial. Eligibility criteria include: histologically confirmed urothelial carcinoma, HER2-negasitive (IHC 0 or 1+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary objectives were activity (ORR) and safety. Progress-free survival, disease control rate and overall survival will also be assessed. Results: As of February 2020, 8 patients were enrolled in the study. The median age was 65 years old. At baseline, most patients (6/8) had visceral metastasis. 6 (75%) patients had received≥2 lines treatment and 4 (50%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 25% (2/8) and the DCR was 75% (6/8). The ORR was 33.3% (2/6) in patients with visceral metastasis and was 50.0% (2/4) in liver metastasis patients. The ORR was 33.3% (2/6) in patients post to ≥ 2 lines of treatment and 25% (1/4) in patients post to immunotherapy. Common treatment-related AEs were AST increase (62.5%), ALT increase (50.0%), nausea (50.0%), leukopenia (37.5%), fatigue (37.5%), vomiting (37.5%), hypoesthesia (25.0%), alopecia (25.0%), and neutropenia (25.0%). Most of these AE were Grade 1 or 2. The AE of Grade 3 was neutropenia (12.5%). The SAE was CPK increased (12.5%). Conclusions: The study showed that RC48-ADC was safety and the ORR was 25% in HER-negative patients with locally advanced or metastatic urothelial carcinoma. Clinical trial information: NCT04073602.