Multicenter phase 1-2 trial of becotatug vedotin plus pucotenlimab for platinum- and immunotherapy-resistant R/M NPC

Patients with recurrent of metastatic nasopharyngeal carcinoma (R/M NPC) have limited therapeutic options after failing platinum and anti-PD-(L)1 therapy. The multicenter phase 1-2 Magic-C001 trial in China evaluated the combination of becotatug vedotin (BV, an EGFR-directed antibody-drug conjugate) and pucotenlimab (PD-1 inhibitor) for these patients. Eligible patients received pucotenlimab 3.0 mg/kg plus BV at 1.8-2.3 mg/kg (phase 1) or 2.0 mg/kg (phase 2) once every 3 weeks. The primary endpoint of phase 2 was objective response rate (ORR). Among 31 patients treated at the recommended phase 2 dose from phase 1 and phase 2, the confirmed ORR was 71.0% (95% CI 52.0-85.5) and the disease control rate was 93.5% (78.6-99.2); the median duration of response was 14.0 months (5.7-NE) and the median progression-free survival was 12.0 months (6.8-15.4). Overall survival data were not mature. The most common treatment-related adverse events were pruritus (71.9%), hypoesthesia (65.6%), anemia (59.4%, and rash (56.3%); grade 3 or 4 TRAEs occurred in 40.6%; no TRAEs led to death. The authors conclude that the combination of BV and pucotenlimab yielded a notable ORR with durable responses and promising PFS, and manageable toxicity, among patients with R/M NPC after failure of platinum and anti-PD-(L)1 therapy.