Becotatug vedotin, MRG003, in previously treated recurrent or metastatic nasopharyngeal carcinoma: A multicenter, single-arm, phase IIa trial

  • Med. 2026 Apr 10;7(4):101029. doi: 10.1016/j.medj.2026.101029.
Fei Han  1 ,  Xing Lv  2 ,  Yu-Juan Zhou  3 ,  Qian He  4 ,  Ye Guo  5 ,  Yan-Qun Xiang  2 ,  Xiao-Lei Shu  6 ,  Su-Ming Pan  7 ,  Shen-Hong Qu  8 ,  Peng Zhang  9 ,  Yi Jiang  10 ,  Ming-Jun Xu  11 ,  Kai-Jian Lei  12 ,  Song Qu  13 ,  Xiao-Hui Wang  4 ,  Yong-Shuai Jin  14 ,  Bei Zhao  14 ,  Rui Dai  14 ,  Feng-Hua Wang  15 ,  Rui-Hua Xu  16
Affiliations
  • 1. Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, P.R. China. Electronic address: [email protected].
  • 2. Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, P.R. China.
  • 3. Head and Neck Radiotherapy Department II, Hunan Cancer Hospital, Changsha 410013, P.R. China.
  • 4. Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou 510060, P.R. China.
  • 5. Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, P.R. China.
  • 6. Oncology Radiotherapy Center, Chongqing University Cancer Hospital, Chongqing 400030, P.R. China.
  • 7. Radiotherapy Department, Yuebei People's Hospital, Shaoguan 512026, P.R. China.
  • 8. Otorhinolaryngology Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, P.R. China.
  • 9. Department of Radiation Oncology, Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu 610041, P.R. China.
  • 10. 2nd Department of Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, P.R. China.
  • 11. Oncology Department, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, P.R. China.
  • 12. Oncology Center, The Second People's Hospital of Yibin, Yibin 644000, P.R. China.
  • 13. 3rd Department of Radiotherapy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi, P.R. China.
  • 14. Lepu Biopharma Co. Ltd., Shanghai 201100, P.R. China.
  • 15. Department of Medical Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China. Electronic address: [email protected].
  • 16. Department of Medical Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China. Electronic address: [email protected].
PMID: 41720100 DOI: 10.1016/j.medj.2026.101029
Abstract

Background: Recurrent/metastatic (R/M) nasopharyngeal carcinoma (NPC) patients who failed platinum-based chemotherapy, with or without PD-1/L1 inhibitors, face limited treatment options. We evaluated the efficacy and safety of MRG003 (becotatug vedotin), an epidermal growth factor receptor (EGFR)-targeted antibody-drug conjugate (ADC), in previously treated R/M NPC.

Methods: This multicenter, single-arm, phase IIa study was part of a phase II trial (NCT05126719). Eligible patients received MRG003 (2.0 or 2.3 mg/kg) intravenously every 3 weeks. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR); disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety were secondary endpoints.

Findings: Sixty-one patients were enrolled with a median follow-up of 21.9 months. IRC-assessed ORR and DCR were 42% (95% confidence interval [CI], 30-56) and 81% (95% CI, 69-90), respectively. Median DoR and PFS were 8.0 months (95% CI, 4.6-not evaluable [NE]) and 5.8 months (95% CI, 3.3-7.6), respectively. Median OS reached 15.8 months (95% CI, 11.0-NE) for all patients and 25.2 months (95% CI, 11.0-NE) for 2.3 mg/kg. Among 33 patients who had failed PD-1/L1 inhibitors and ≥2 prior chemotherapy lines, ORR and DCR were 30% and 76%, respectively. Grade ≥3 treatment-related adverse events occurred in 24 patients (39%). No treatment-related deaths occurred.

Conclusions: MRG003 demonstrated promising efficacy and manageable safety in pretreated R/M NPC patients. This is also the first long-term evaluation of an EGFR-targeted ADC in this population.

Funding: Study was supported by Shanghai Miracogen Inc, one subsidiary of Lepu Biopharma Co., Ltd.

Keywords
antibody-drug conjugate; becotatug vedotin; objective response rate; recurrent/metastatic nasopharyngeal carcinoma; translation to patients.
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