Becotatug Vedotin Combined With Pucotenlimab in Platinum- and Immunotherapy-Resistant Recurrent or Metastatic Nasopharyngeal Carcinoma
Mené sur 31 patients atteints d'un carcinome récidivant ou métastatique du rhinopharynx, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant bécotatug védotin (un conjugué anticorps-médicament ciblant EGFR) et pucotenlimab (un inhibiteur de PD-1)
Purpose: Patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) have limited therapeutic options after failing platinum and anti–PD-1/PD-L1 therapy. We investigated the efficacy and safety of an epidermal growth factor receptor (EGFR)–directed antibody-drug conjugate (ADC) becotatug vedotin (BV) combined with a PD-1 inhibitor pucotenlimab in this setting of patients.
Materials and Methods: Magic-C001 (ClinicalTrials.gov identifier: NCT05688605) is an ongoing, open-label, multicohort, dose escalation (phase I) and expansion (phase II) study in patients with EGFR-positive solid tumors. Eligible patients received pucotenlimab 3.0 mg/kg and BV at 1.8-2.3 mg/kg (phase I) or 2.0 mg/kg (phase II for NPC) once every 3 weeks. The primary end point for phase II was objective response rate (ORR). Secondary end points included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
Results: Among 31 patients with NPC at the recommended phase II dose (RP2D) from phase I and II who had received anti–PD-1/PD-L1 and platinum-based therapy, the confirmed ORR was 71.0% (95% CI, 52.0 to 85.8); DCR was 93.5% (95% CI, 78.6 to 99.2). The median DoR and PFS were 14.0 months (95% CI, 5.7 to not estimated) and 12.0 months (95% CI, 6.8 to 15.4), respectively. Median OS was not mature. Most common treatment-related adverse events (TRAEs) were pruritus (71.9%), hypoesthesia (65.6%), anemia (59.4%), and rash (56.3%). TRAEs of ≥grade 3 occurred in 40.6% of patients. No TRAEs led to death.
Conclusion: To our knowledge, we report the first trial combining an ADC with immunotherapy for platinum and anti–PD-1/PD-L1–resistant NPC. BV plus pucotenlimab yielded a notable ORR with exceptionally durable responses and substantially prolonged PFS, alongside manageable toxicities. This regimen may offer a promising anti–PD-1 rechallenge strategy in this population, which is being confirmed in an ongoing, multicenter, randomized controlled, phase III study.
Journal of Clinical Oncology , résumé, 2026