In October 2025, becotatug vedotin (Meiyouheng®), developed by Lepu Biopharma, received marketing approval from the National Medical Products Administration (NMPA) in China for the treatment of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) in adults who have failed at least two lines of systemic chemotherapy and PD-1/PD-L1 inhibitor therapy. As the first Epidermal Growth Factor Receptor (EGFR)-targeted antibody-drug conjugate (ADC) approved for this indication in China, it represents a significant milestone in NPC management and offers new hope for patients with refractory disease.*
Nasopharyngeal carcinoma (NPC) is an aggressive, radiosensitive head and neck malignancy arising from the epithelial lining of the nasopharynx, most commonly in the fossa of Rosenmüller.** For patients with recurrent or metastatic disease, treatment options are limited. NPC is an epithelial tumor of the nasopharynx and is strongly associated with Epstein‑Barr virus (EBV) infection. Although radiotherapy alone can cure ~90% of patients with early‑stage disease, >70% of patients with NPC have locoregionally advanced or metastatic disease at the first diagnosis due to the insidious and aggressive nature of NPC.[1] Furthermore, recurrent/metastatic (R/M) nasopharyngeal carcinoma patients who failed platinum-based chemotherapy, with or without PD-1/L1 inhibitors, face limited treatment options. [2][3]
EGFR is highly expressed in advanced NPC, making it an attractive therapeutic target. Becotatug vedotin is the first EGFR-targeted ADC approved for use in China, demonstrating first-in-class potential.
Mechanism of Action
Becotatug vedotin combines an EGFR-targeted monoclonal antibody with monomethyl auristatin E (MMAE), a potent microtubule inhibitor, via a valine-citrulline linker. After binding and internalization by EGFR-expressing tumor cells, lysosomal cleavage releases the cytotoxic payload, leading to tumor cell death.
In multicenter phase II trials, becotatug vedotin showed significant efficacy in heavily pretreated R/M NPC patients:
- Objective Response Rate (ORR): 42% (95% CI 30-56)
- Disease Control Rate (DCR): 81% (95% CI 69-90)
- Median Duration of Response (DoR): 8.0 months
- Median Progression-Free Survival (PFS): 5.8 months
- Median Overall Survival (OS): 15.8 months (all patients); 25.2 months (2.3 mg/kg cohort)
Among patients who failed PD-1/PD-L1 inhibitors and ≥2 prior chemotherapy lines, ORR was 30% and DCR 76%. No treatment-related deaths occurred; grade ≥3 treatment-related adverse events were seen in 39% of patients. Combination therapy with the anti-PD-1 agent pucotenlimab further enhanced efficacy, achieving an ORR of 73.3% and a median PFS of 10.9 months in patients who had failed immunotherapy and platinum-based therapy. In the first-line setting for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN), ORR reached 60% in the higher dose cohort, with durable responses and manageable safety.
Significance and Future Directions
The approval of becotatug vedotin marks a milestone as the first EGFR-targeted ADC for R/M NPC in China. It offers a new option for patients with limited alternatives and is poised for further investigation in additional indications and combinations, including head and neck cancers. Ongoing randomized trials will clarify optimal dosing and long-term outcomes.
Becotatug vedotin provides clinically meaningful responses and a manageable safety profile in patients with recurrent/metastatic NPC who have exhausted standard therapies. Its approval signals a new era for ADCs in China and advances targeted therapeutics for EGFR-expressing malignancies.
In ongoing studies, becotatug vedotin is investigated in combination with pucotenlimab (Puyouheng™)***, a novel, humanized IgG4 monoclonal antibody that acts as an immune checkpoint inhibitor and binds to the PD-1 receptor to restore the immune system’s ability to detect and destroy cancer cells. As a first-line treatment in recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN), the combination showed an encouraging and durable antitumor activity and a manageable safety profile,warranting additional studies.
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Note:* Becotatug vedotin was granted Orphan Drug Designation by the US Food and Drug Administration (FDA) in September 2022 for the treatment of nasopharyngeal carcinoma (NPC).
** The fossa of Rosenmüller (also known as the pharyngeal recess) is a deep, mucosal-lined pocket in the roof of the nasopharynx, located just behind the Eustachian tube opening. It is clinically significant as the most common site of origin for nasopharyngeal carcinomas and benign retention cysts.
*** Developed by Lepu Biopharma, but originally discovered by Akeso/HanX, is approved in China, where it is conditionally approved by the National Medical Products Administration (NMPA) for treating specific advanced solid tumors.
Clinical trial
A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma – ClinicalTrials.gov ID NCT05126719
A Study of MRG003 in the Treatment of Patients With EGFR-positive Advanced or Metastatic Solid Tumors
ClinicalTrials.gov ID NCT05688605
Reference
[1] Huang H, Yao Y, Deng X, Huang Z, Chen Y, Wang Z, Hong H, Huang H, Lin T. Immunotherapy for nasopharyngeal carcinoma: Current status and prospects (Review). Int J Oncol. 2023 Aug;63(2):97. doi: 10.3892/ijo.2023.5545. Epub 2023 Jul 7. PMID: 37417358; PMCID: PMC10367053.
[2] Han F, Lv X, Zhou YJ, He Q, Guo Y, Xiang YQ, Shu XL, Pan SM, Qu SH, Zhang P, Jiang Y, Xu MJ, Lei KJ, Qu S, Wang XH, Jin YS, Zhao B, Dai R, Wang FH, Xu RH. 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. PMID: 41720100.
[3] Blair HA. Becotatug Vedotin: First Approval. Drugs. 2026 Apr;86(4):573-579. doi: 10.1007/s40265-026-02290-5. Epub 2026 Mar 6. PMID: 41787195.
[4] Xue L, Han Y, Zhang Q, Li X, Fang M, Zhong L, Wang S, Liu Y, Zhang S, Li Z, Guo Y. Becotatug Vedotin in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: A Multicenter, Phase IIa Trial. Clin Cancer Res. 2026 Apr 15;32(8):1445-1453. doi: 10.1158/1078-0432.CCR-25-3930. PMID: 41603720.
[5] Li Z, Zhou Y, Lin J … 1389P Preliminary results of phase II study to evaluate safety and efficacy of becotatug vedotin in combination with pucotenlimab as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) Annals of Oncology, 36S797
Featured image and image in article: Nasopharyngeal Carcinoma (explanatory). Image courtesy: © 2026 Sunvalley Communication. Used with permission.
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