A single-arm, multicenter, phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate (MRG002) in HER2-positive unresectable locally advanced or metastatic urothelial carcinoma

• Published in: European journal of cancer (1990) Vol. 205; p. 114096
• Main Authors: Qu, Wang, Fu, Cheng, Han, Weiqing, Luo, Hong, Quan, Jizhong, Chen, Lijun, Liao, Yong, Hu, Changlu, Hu, Hailong, Niu, Yinong, Xu, Danfeng, Chen, Minfeng, Chen, Jimin, Liu, Yongda, Chen, Guojun, Luo, Zhanxiong, Shi, Benkang, Sun, Yongkun, Zhou, Fangjian, Zhou, Aiping
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2024
• Subjects: ADC; HER2; Urothelial carcinoma; ADC; HER2; Urothelial carcinoma
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.114096

MRG002 is a novel HER2-targeted antibody-drug conjugate being investigated in the MRG002–006 trial to evaluate the efficacy and safety in HER2-positive urothelial carcinoma patients. This is an open-label, single-arm, multicenter phase II study. Eligibility criteria included: histologically confirmed HER2 IHC 2 + or 3 + UC, prior received ≥ 1 standard treatment. Patients in this study received MRG002 every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST 1.1. As of February 24, 2023, a total of 43 patients were enrolled. The median age was 60. 9 patients were dosed at 2.6 mg/kg and 34 patients were dosed at 2.2 mg/kg. At baseline, most patients (29/43) received ≥ 2 lines of treatment and 35 (81.4%) patients had prior ICI therapy. FISH test was performed in 41 patients and 9 (22.0%) were positive. By the cut-off date, 41 patients were evaluable and the ORR was 53% (95%CI：38.9%−67.5%), with 6.9% CR, and the DCR was 83.7% (95%CI：70.0%−91.9%). The median PFS and OS for the 43 patients were 7.0 months (95%CI：5.4-NE) and 14.9 months (95%CI：11.9-NE), respectively. The ORR was 77.8% in 9 patients with positive HER2 FISH results. Most common treatment-related AEs were anemia (51.2%), alopecia (44.2%) and neutropenia (39.5%); most were grade 1 or 2. Preliminary results of MRG002 demonstrated a clinically meaningful response in pretreated HER-2 positive unresectable locally advanced or metastatic UC patients. MRG002 at 2.2 mg/kg was well tolerated with a manageable toxicity. •MRG002 is a novel HER2-targeted ADC.•MRG002 monotherapy in the later-line showed an ORR of 53% in HER2 2/3 + UC pts.•MRG002 at 2.2 mg/kg was well tolerated and most AE were grade 1 or 2.•MRG002 could be another promising ADC in HER-2 positive UC.