The combination of the epidermal growth factor receptor (EGFR)–directed antibody-drug conjugate (ADC) becotatug vedotin and the PD-1 inhibitor pucotenlimab demonstrated antitumor activity in patients with recurrent or metastatic nasopharyngeal carcinoma previously treated with platinum-based therapy and PD-1/PD-L1 inhibitors, according to results from the phase I/II Magic-C001 study reported by Ruan et al in the Journal of Clinical Oncology.
Study Details
Magic-C001 (ClinicalTrials.gov identifier NCT05688605) is an open-label, multicenter phase I/II study conducted at 13 hospitals in China evaluating becotatug vedotin plus pucotenlimab in patients with EGFR-positive advanced solid tumors. The study included phase I dose escalation followed by phase II dose expansion. Patients with recurrent or metastatic nasopharyngeal carcinoma enrolled in phase II were required to have experienced disease progression following first-line platinum-based therapy.
Patients received pucotenlimab at 3.0 mg/kg plus becotatug vedotin every 3 weeks. Becotatug vedotin was evaluated at multiple doses during phase I, with 2.0 mg/kg selected as the recommended phase II dose. The primary endpoint of phase II was objective response rate; secondary endpoints included duration of response, disease control rate, progression-free survival, overall survival, and safety.
The efficacy analysis included 31 patients treated at the recommended phase II dose who had previously received both platinum-based therapy and anti–PD-1/PD-L1 therapy. The median age of the overall 32-patient safety population was 49 years (range = 31–64 years). Nine patients (28.1%) had previously received an EGFR-targeted monoclonal antibody.
Key Results
At the data cutoff of September 17, 2025, 28 of 31 efficacy-evaluable patients experienced targeted lesion shrinkage. Two patients achieved a confirmed complete response and 20 achieved a confirmed partial response, resulting in an objective response rate of 71.0% (95% confidence interval [CI] = 52.0%–85.8%). Seven additional patients had stable disease, for a disease control rate of 93.5% (95% CI = 78.6%–99.2%).
Among the 22 responders, the median duration of response was 14.0 months (95% CI = 5.7 months–not estimated), with 10 responses ongoing at data cutoff. Median progression-free survival was 12.0 months (95% CI = 6.8–15.4 months). After a median follow-up of 18.8 months, the 12- and 18-month overall survival rates were 93.3% and 82.5%, respectively.
All 32 patients in the safety population experienced at least one treatment-related adverse event, with grade 3 or higher events occurring in 13 patients (40.6%). The most common treatment-related adverse events were pruritus (71.9%), hypoesthesia (65.6%), anemia (59.4%), and rash (56.3%), all of which were grade 1 or 2. Treatment-related serious adverse events occurred in 25.0% of patients, and no treatment-related adverse events resulted in death.
The investigators concluded: “To our knowledge, we report the first trial combining an ADC with immunotherapy for platinum and anti–PD-1/PD-L1–resistant [nasopharyngeal carcinoma]. [Becotatug vedotin] plus pucotenlimab yielded a notable [objective response rate] with exceptionally durable responses and substantially prolonged [progression-free survival], 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.”
Rui-Hua Xu, MD, of the Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Shanghai Miracogen Inc. For full disclosures of the study authors, visit ascopubs.org.
