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
  • 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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