2. Academic Validation
  3. 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

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

  • Eur J Cancer. 2024 Jul:205:114096. doi: 10.1016/j.ejca.2024.114096.
Wang Qu 1,  Cheng Fu 2,  Weiqing Han 3,  Hong Luo 4,  Jizhong Quan 5,  Lijun Chen 6,  Yong Liao 7,  Changlu Hu 8,  Hailong Hu 9,  Yinong Niu 10,  Danfeng Xu 11,  Minfeng Chen 12,  Jimin Chen 13,  Yongda Liu 14,  Guojun Chen 15,  Zhanxiong Luo 16,  Benkang Shi 17,  Yongkun Sun 1,  Fangjian Zhou 18,  Aiping Zhou 19
Affiliations

Affiliations

  • 1 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 2 Department of Urological Surgical Oncology, Liaoning Cancer Hospital and Institute, Shenyang 110042, China.
  • 3 Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Center, Changsha 410031, China.
  • 4 Department of Genitourinary Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, China.
  • 5 Department of Radiotherapy, Jilin Guowen Hospital, Siping 136199, China.
  • 6 Department of Urology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100039, China.
  • 7 Department of Urology, Sichuan Provincial People's Hospital, Chengdu 610072, China.
  • 8 Department of Medical Oncology, Anhui Cancer Hospital, Hefei 230031, China.
  • 9 Department of Urology, Tianjin Medical University Second Hospital, Tianjin 300211, China.
  • 10 Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020,China.
  • 11 Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
  • 12 Department of Urology, Xiangya Hospital Central South University, Changsha 410008, China.
  • 13 Department of Urology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310003, China.
  • 14 Department of Urology, The First Affiliated Hospital Guangzhou Medical University, Guangzhou 510120, China.
  • 15 Department of Urology, Qinghai University Affiliated Hospital, Xining 810001, China.
  • 16 Department of Medical Oncology, Liuzhou People's Hospital, Liuzhou 545006, China.
  • 17 Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, China.
  • 18 Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China. Electronic address: [email protected].
  • 19 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: [email protected].
PMID: 38772302 DOI: 10.1016/j.ejca.2024.114096
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

ADC; HER2; Urothelial carcinoma.

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