Efficacy and safety of liposomal irinotecan plus nimotuzumab in immune checkpoint inhibitor-refractory recurrent or metastatic nasopharyngeal carcinoma: a single-arm, open-label, phase II trial

Background Patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) who progress after immune checkpoint inhibitor (ICI) therapy have limited treatment options and poor outcomes. We evaluated the efficacy and safety of liposomal irinotecan plus nimotuzumab in patients with epidermal growth factor receptor (EGFR)-positive, ICI-refractory R/M NPC. Methods In this single-arm, open-label, phase II trial (NCT06414577) conducted in China, patients with EGFR-positive, ICI-refractory R/M NPC were enrolled between May 27, 2024, and January 9, 2025. Patients received intravenous liposomal irinotecan (70 mg/m 2 ) plus nimotuzumab (400 mg) every 2 weeks for up to eight cycles. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Findings Thirty-six heavily pretreated patients were enrolled, of whom 12 (33.3%) had received three or more prior lines of therapy for advanced disease. In the intention-to-treat population, 13 of 36 patients achieved an objective response (ORR 36.1%; 95% CI 20.8–53.8), and 22 of 36 patients achieved disease control (61.1%). Median progression-free survival was 3.0 months (95% CI, 2.2–4.1), and median duration of response was 2.3 months (95% CI 1.5–3.1). After a median follow-up of 22.0 months, the median overall survival was 14.1 months (95% CI, 8.7-not estimable). Grade 3 or higher treatment-related adverse events occurred in eight of 36 patients (22.2%), and no treatment-related deaths were observed. In a post-hoc exploratory analysis, an early decline of at least 50% in plasma Epstein–Barr virus DNA was associated with a higher ORR. Interpretation Liposomal irinotecan plus nimotuzumab showed preliminary antitumor activity and manageable safety in heavily pretreated patients with ICI-refractory R/M NPC. However, response durability was limited, and further comparative studies are needed to evaluate its clinical value and identify patients most likely to derive durable benefit. Funding Supported by grants from the National Natural Science Foundation of China, Science and Technology Program of Guangdong Esophageal Cancer Institute, and China Postdoctoral Science Foundation.