Efficacy and safety of HLX43 (an anti–PD-L1 ADC) in previously treated recurrent/metastatic nasopharyngeal carcinoma: A multicenter, randomized phase 2 study.

Abstract

6060 Background: Treatment options are limited and clinical outcomes remain unsatisfactory for patients with recurrent/metastatic nasopharyngeal carcinoma (r/m NPC) in the later-line setting. HLX43 is a novel anti-programmed cell death-ligand 1 (PD-L1) antibody-drug conjugate with promising antitumor activity in advanced tumors. Here we present results from a phase 2 study evaluating HLX43 in previously treated r/m NPC. Methods: This randomized, multicenter trial enrolled patients with histologically or cytologically confirmed r/m NPC who had received at least second-line chemotherapy (including one prior line of platinum-based chemotherapy) and progressed on or were intolerant to programmed death (ligand) 1 (PD-[L]1) inhibitor. Patients were randomized 1:1:1 to receive 2 mg/kg, 2.5 mg/kg, or 3 mg/kg of intravenous HLX43 every 3 weeks. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) per investigator's assessments. Results: As of September 18, 2025, 30 patients were randomized to the 2, 2.5, or 3 mg/kg group ( n = 10 for each group). The median follow-up duration was 2.8 months (range 2.1–5.6). Twenty-six patients (86.7%) had performance status 1; 27 (90.0%) had prior radiotherapy. The median line of prior systemic therapy was 3 (range 2–8). ORR was 36.7%, with partial responses (PRs) in 11 patients. ORR in the three dose groups was 20.0%, 20.0% and 70.0% (all confirmed by December 2025), respectively; disease control rate (DCR) was 50.0%, 50.0% and 80.0%. PFS data were immature. Overall, treatment-emergent adverse events (TEAEs) occurred in 29 patients (96.7%; grade ≥3, 50.0%). TEAE incidence was 90.0%, 100% and 100% in the three dose groups, respectively. TEAE leading to dose reduction was reported in 3 patients (30.0%) in the 3 mg/kg group only. TEAE leading to treatment discontinuation occurred in 1 (10.0%) each in the 2.5 mg/kg and 3 mg/kg groups. There was no death due to TEAE. The efficacy and safety findings are detailed in Table 1. Conclusions: HLX43 showed promising efficacy with a manageable safety profile in r/m NPC patients who had progressed after second-line or later chemotherapy and PD-(L)1 inhibitors. Further investigation is warranted. Clinical trial information: NCT06839066 . Efficacy and safety. 2.0 mg/kgN=10 2.5 mg/kgN=10 3.0 mg/kgN=10 TotalN=30 PR 2 (20.0) 2 (20.0) 7 (70.0) 11 (36.7) SD 3 (30.0) 3 (30.0) 1 (10.0) 7 (23.3) PD/NE 5 (50.0) 5 (50.0) 2 (20.0) 12 (40.0) ORR, 95% CI (%) 20.0(2.5, 55.6) 20.0(2.5, 55.6) 70.0(34.8, 93.3) 36.7(19.9, 56.1) DCR, 95% CI (%) 50.0(18.7, 81.3) 50.0(18.7, 81.3) 80.0(44.4, 97.5) 60.0(40.6, 77.3) TEAEs 9 (90.0) 10 (100) 10 (100) 29 (96.7) Grade ≥3 TEAEs 2 (20.0) 7 (70.0) 6 (60.0) 15 (50.0) TEAE leading to dose reduction 0 0 3 (30.0) 3 (10.0) TEAE leading to treatment discontinuation 0 1 (10.0) 1 (10.0) 2 (6.7) NE, not evaluable. PD, progressive disease. SD, stable disease.