Background
Multicenter, open-label, randomised trial; N=173; recurrent/metastatic nasopharyngeal carcinoma after ≥2 lines including chemotherapy and PD-1/PD-L1 inhibitors. Becotatug vedotin (MRG003) = first-in-class anti-EGFR antibody-drug conjugate (MMAE payload). Tests becotatug vedotin vs investigator-choice chemotherapy in a setting with no established standard of care.
Results
Interventions and follow up: Arm A: Becotatug vedotin 2.3 mg/kg IV q3w, n=86
Arm B: Chemotherapy (capecitabine or docetaxel), n=87
Primary endpoint: ORR, PFS and OS (co-primary; independent review committee)
mFollow up: 7.4 mo (PFS); 13.5 mo (interim OS)
Results: ORR: 30.2% vs 11.5%; P=.003
PFS: 5.82 vs 2.83 mo; HR 0.63 (95% CI 0.43–0.91); P=.01
OS (interim): 17.08 vs 11.99 mo; HR 0.73 (95% CI 0.48–1.12); P=.15 (immature)
Arm B: Chemotherapy (capecitabine or docetaxel), n=87
Primary endpoint: ORR, PFS and OS (co-primary; independent review committee)
mFollow up: 7.4 mo (PFS); 13.5 mo (interim OS)
Results: ORR: 30.2% vs 11.5%; P=.003
PFS: 5.82 vs 2.83 mo; HR 0.63 (95% CI 0.43–0.91); P=.01
OS (interim): 17.08 vs 11.99 mo; HR 0.73 (95% CI 0.48–1.12); P=.15 (immature)
Adverse events
Overall: safety profiles comparable between arms
Becotatug vedotin (MMAE ADC) class effects: EGFR-related skin toxicity/rash, peripheral neuropathy, cytopenias (grade-specific rates NR in primary report)
Becotatug vedotin (MMAE ADC) class effects: EGFR-related skin toxicity/rash, peripheral neuropathy, cytopenias (grade-specific rates NR in primary report)
Conclusions
In heavily pretreated, immunotherapy-exposed R/M nasopharyngeal carcinoma, becotatug vedotin nearly tripled ORR and significantly improved PFS vs chemotherapy, with comparable toxicity and encouraging but immature OS. First randomized evidence for an EGFR-directed ADC in NPC.
Key Limitations
Open-label; modest sample (N=173) with short PFS follow-up and immature, non-significant OS (HR 0.73, P=.15); investigator-choice single-agent chemotherapy comparator of limited efficacy in this setting; conducted in China/endemic NPC, limiting generalizability to non-endemic disease; grade-specific adverse-event rates not detailed in the primary report.
Clinical Context
Becotatug vedotin received first approval in China (NMPA, Oct 2025) for R/M NPC after ≥2 prior lines including platinum chemotherapy and PD-1/PD-L1 inhibitors; not FDA/EMA approved. It addresses an unmet need where no standard exists after platinum + immunotherapy failure and is the first EGFR-targeted ADC to show randomized benefit in NPC (ASCO 2025 late-breaking, LBA6005).