Lepu Biopharma’s Becotatug vedotin (MRG003) is an innovative antibody-drug conjugate (ADC) designed to target EGFR. Data presented at ASCO 2025 brings hope for heavily pretreated recurrent or metastatic (R/M) Nasopharyngeal carcinoma (NPC) progressing after platinum and  PD-1 inhibitors. NPC is a distinct malignancy of the head and neck, with the endemic subtype strongly associated with Epstein-Barr virus (EBV) infection. Emerging evidence indicates that human papillomavirus (HPV) may play a role in a subset of nonendemic cases.

At this year's ASCO Annual Meeting, Becotatug Vedotin presented key clinical research data for the first time (this abstract was selected for an LBA oral presentation). 

By June 30, 2024, the BICR-evaluated ORR for the Becotatug Vedotin group was 30.2%, while the ORR for the chemotherapy group was 11.5%, almost three times the value. With a 37% reduction in the risk of disease progression or death (5.82 months vs. 2.83 months; HR=0.63, p=0.0146), the median PFS benefit doubled.

The median overall survival (OS) for the two patient groups was 17.08 months vs. 11.99 months (HR=0.73) as of December 30, 2024, at the interim analysis. A clear trend of benefit was demonstrated by Becotatug Vedotin. The OS HR of the two groups was 0.59 (95% CI 0.37-0.93) when the effect of cross-treatment was excluded, making the survival benefit more apparent. Regarding safety, there was no significant difference in the frequency of treatment-related adverse events (TRAEs) between the Becotatug Vedotin and chemotherapy groups. The incidence of grade ≥3 TRAEs was 50.6%, while the majority of adverse events were grade 1–2.

KOL insights: 

“At this year's ASCO Annual Meeting, the key registration clinical study of Becotatug Vedotin once again demonstrated China's innovative strength. Compared with chemotherapy, Becotatug Vedotin has a clear benefit in ORR in patients with recurrent or metastatic NPC who have previously failed ≥2 lines of systemic chemotherapy and PD-(L)1 inhibitors, with a nearly three-fold increase in ORR, a doubling of PFS, and a clear OS benefit trend and good safety, providing a better choice for the second-line treatment of NPC patients and filling unmet clinical needs”. – Expert Opinion

Conclusion:

DelveInsight estimates that there were around 2,100 NPC cases in the United States in 2024. LOQTORZI (toripalimab-tpzi), a next-generation PD-1 inhibitor is the only available US Food and Drug Administration (FDA)-approved treatment indicated in combination with chemotherapy for recurrent or metastatic NPC, and it is in development for the treatment of additional tumor types with the goal of being the PD-1/ICI backbone of future treatment combinations that may extend survival for patients. Immunotherapy combined with chemotherapy has become the standard treatment for patients with advanced NPC in the clinic, but there is still a lack of standard follow-up treatment options. 

An important milestone in China's transformation to an "Innovation Powerhouse" took place when the US FDA certified becotatug vedotin as a breakthrough drug for the treatment of R/M NPC. Becotatug Vedotin is presently being evaluated in China and is anticipated to be the first EGFR ADC authorized for commercialization globally.

This is the first randomized controlled study to publish the efficacy results of EGFR ADC in patients with recurrent or metastatic nasopharyngeal carcinoma who have received at least two lines of treatment.  This study could drive a paradigm shift in R/M NPC treatment. It is important to note that more ADCs are being extensively studied in the same setting.