Preliminary results of a phase Ib/II combination study of RC48-ADC, a novel humanized anti-HER2 antibody-drug conjugate (ADC) with toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with locally advanced or metastatic urothelial carcinoma.

作者：Xinan Sheng, Li Zhou, Zhisong He, Hongqian Guo, Xieqiao Yan, Siming Li, Huayan Xu, Juan Li, Zhihong Chi, Lu Si, Chuanliang Cui, Lili Mao, Bin Lian, Bixia Tang, Xuan Wang, Xue Bai, Jun Guo · 发表于：Journal of Clinical Oncology · 年份：2022 · DOI：10.1200/jco.2022.40.16_suppl.4518 · 被引用次数：28 · 研究领域：Bladder and Urothelial Cancer Treatments、Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers

4518 Background: RC48-ADC has shown promising data in HER2-positive and even negative patients with metastatic urothelial carcinoma (mUC) who failed with platinum-based chemotherapy. RC48-ADC combined with anti-PD-1 antibody may have a synergistic antitumor effect. Methods: This is an open-label, multicenter, phase 1b/II trial to evaluate the safety and activity of RC48 combined with toripalimab in mUC. Patients received RC48-ADC at 1.5 or 2 mg/kg, in combination with 3mg/kg toripalimab every two weeks in a dose-escalation and expansion cohort until confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. The key primary endpoint was safety; secondary endpoints included efficacy and tumor tissue biomarkers. Results: As of 17 Jan 2022 (data cutoff), 41 la/mUC pts (19 males; median age 66 y [42-76]) were enrolled since 20 Aug 2020. 61% patients were systemic treatment naïve, and 54% had visceral metastases (mets), including 24% with liver mets. The primary site was in upper tract UC in 54%. HER2 expression was positive (IHC 2+ or 3+) in 59% patients, and PD-L1 positive (CPS ≥ 10) in 32%. No dose-limiting toxicity was observed. The recommended dose was RC48-ADC 2mg/kg + toripalimab 3mg/kg every 2 weeks. With a median follow-up of 8.0 mos, 36 patients had at least one tumor assessment, the best ORR was 83.3%, and the confirmed ORR was 76.7% (95%CI: 57.7, 90.1), including 10% CR. The cORR was 82.4% for 1L previously untreated mUC patients, 100% for patients w...