Becotatug vedotin for recurrent/metastatic nasopharyngeal carcinoma (Magic-M001): a multicenter, randomized trial.

BACKGROUND

Patients with recurrent/metastatic nasopharyngeal carcinoma (NPC) had limited treatment option and dismal prognosis after failure to programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors and chemotherapy.

PATIENTS AND

METHODS

This multicenter, open-label, randomized trial investigated the anti-epidermal growth factor receptor antibody-drug conjugate becotatug vedotin in patients with recurrent/metastatic NPC after failure to ≥2 lines of systemic therapies, including chemotherapy and PD-1/PD-L1 inhibitors. Eligible participants were randomly assigned 1:1 to receive becotatug vedotin 2.3 mg/kg every 3 weeks or chemotherapy (capecitabine or docetaxel). The coprimary endpoints were the independent review committee-confirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

RESULTS

Between 6 April 2023 and 27 December 2023, a total of 173 patients were randomly assigned, with 86 assigned to becotatug vedotin and 87 to chemotherapy. As of 30 June 2024, the ORR was significantly higher with becotatug vedotin than with chemotherapy (30.2% versus 11.5%, P = 0.003). With a median follow-up of 7.39 months, becotatug vedotin was associated with a significantly reduced risk of disease progression or death compared with chemotherapy [median PFS, 5.82 versus 2.83 months; hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.43-0.91, log-rank P = 0.01]. As of 30 December 2024, the interim OS analysis showed a median OS of 17.08 months with becotatug vedotin and 11.99 months with chemotherapy (HR 0.73, 95% CI 0.48-1.12, log-rank P = 0.15), with a median follow-up of 13.47 months. The safety profiles were comparable between treatment groups.

CONCLUSIONS

Among patients with heavily pretreated and immunotherapy-exposed recurrent or metastatic NPC, becotatug vedotin significantly improved ORR and PFS compared with chemotherapy, with comparable toxicity and encouraging but immature OS results.