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. Epub 2026 Feb 19.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • ErbB Receptors / antagonists & inhibitors
  • Female
  • Humans
  • Immunoconjugates* / administration & dosage
  • Immunoconjugates* / adverse effects
  • Immunoconjugates* / therapeutic use
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma* / drug therapy
  • Nasopharyngeal Carcinoma* / mortality
  • Nasopharyngeal Carcinoma* / pathology
  • Nasopharyngeal Neoplasms* / drug therapy
  • Nasopharyngeal Neoplasms* / mortality
  • Nasopharyngeal Neoplasms* / pathology
  • Neoplasm Recurrence, Local* / drug therapy
  • Progression-Free Survival

Substances

  • Immunoconjugates
  • ErbB Receptors