First-line HLX07 vs placebo combined with serplulimab and chemotherapy for nasopharyngeal carcinoma: A randomized, double-blind, multicenter phase 2 study.

6042 Background: Programmed cell death protein 1 (PD-1) blockade with chemotherapy confers significant survival benefit compared to chemotherapy alone and is the standard first-line therapy for recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). Epidermal growth factor receptor (EGFR) is overexpressed in approximately 85% of all NPCs and associated with poor outcomes, suggesting a potential target for improved efficacies. This study explores the efficacy of HLX07 (a novel humanized anti-EGFR antibody) versus placebo, in combination with serplulimab (PD-1 inhibitor) and chemotherapy as first-line treatment for R/M-NPC. Methods: This is a randomized, double-blind, multicenter phase 2 study. Patients with histopathologically confirmed, unresectable, R/M NPC that is not amenable to local or radical treatment and had no prior systemic therapy were randomized 2:1 to receive either HLX07 at 1000 mg (HLX07 group) or placebo (placebo group), along with serplulimab (300 mg) and chemotherapy (gemcitabine and cisplatin) Q3W intravenously. Primary endpoint was blinded independent central review (BICR)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics and biomarker explorations. Results: As of December 24, 2025, 75 patients were randomized to the HLX07 group (n=50) or placebo group (n=25). Efficacy results are reported for the per-protocol set (n = 72), which excluded two patients who violated the enrolment criteria and one with no post-baseline tumor assessment in the HLX07 group. With 26.0 months of follow-up, BICR-assessed confirmed ORR was 74.5% vs. 72.0% for the two groups. Overall, a trend of an improved median progression-free survival (PFS) was observed with HLX07 (17.3 months vs. 9.4 months, stratified hazard ratio HR 0.79, 95% CI 0.40–1.56). Median overall survival was not reached vs. 27.9 months (stratified HR 0.40, 95% CI 0.16–0.99) for the respective groups. Subgroup analysis revealed a trend of improved PFS in the HLX07 group compared to the placebo group for patients with PD-L1 CPS <10 (median PFS, 8.1 vs. 6.8 months, HR 0.54, 95% CI 0.19–1.56) as well as for patients with EGFR H-score ≥200 (median PFS, not reached vs. 7.8 months, HR 0.30, 95% CI 0.08–1.15). 74 (98.7%) patients experienced treatment-emergent adverse events (TEAEs), with grade ≥3 TEAEs reported in 60 (80.0%) patients. TEAEs led to treatment discontinuation occurred in 14 (18.7%) patients. Deaths due to TEAEs were reported in 5 (6.7%) patients, with 1 (1.3%) in the HLX07 group that was treatment related. Conclusions: The addition of HLX07 to serplulimab and chemotherapy showed encouraging efficacy along with a manageable safety profile in patients with treatment-naïve R/M-NPC. Further investigation of this treatment regimen is warranted. Clinical trial information: NCT05513573 .