Efficacy and safety of HLX43 (anti–PD-L1 ADC) in patients with advanced non–small cell lung cancer.

8512 Background: HLX43 (a PD-L1 ADC) has demonstrated encouraging efficacy with a manageable safety in a phase 1 study. Here, we present the pooled findings from patients with NSCLC in a phase 1 study (HLX43-FIH101) as well as a global phase 2 study investigating HLX43 in NSCLC (HLX43-NSCLC201). Methods: The phase 1 study included a dose-escalation phase in patients with advanced solid tumors (0.5–4.0 mg/kg Q3W), followed by a dose-expansion phase in patients with advanced or metastatic NSCLC at doses of 2.0, 2.5, and 3.0 mg/kg Q3W. The phase 2 study was conducted in NSCLC and comprised two parts: Part A was dose-exploration for patients who had failed prior first-line therapy and had no actionable genomic alterations, to receive HLX43 at 2.0 or 2.5 mg/kg Q3W; Part B was dose-expansion in which patients received HLX43 at the recommended dose determined from Part A. This analysis integrated data from heavily pretreated NSCLC patients enrolled across both studies. Efficacy and safety outcomes were evaluated in the pooled population. Results: As of December 31, 2025, 205 patients were enrolled and received HLX43 at 1 mg/kg (n = 3), 2 mg/kg (n = 89), 2.5 mg/kg (n = 85), 3 mg/kg (n = 23), and 4 mg/kg (n = 5). Patients received a median of 2 lines of prior antitumor therapy (range, 1–9). Among the 161 response-evaluable patients (2, 69, 64, 21, and 5 in the 1, 2, 2.5, 3, and 4 mg/kg groups, respectively), the investigator-assessed ORR was 31.1%. In the 2.0 mg/kg group, investigator-assessed ORR was 36.4% for squamous NSCLC (n = 33); among these patients, ORR was 40.0% for those who previously failed docetaxel (n = 15). ORR was 47.4%, and 50.0% for patients with EGFR-wildtype (n = 19), and EGFR-mutant (n = 16) nonsquamous NSCLC receiving HLX43 at 2.5 mg/kg. Biomarker exploratory analyses showed that efficacy was not associated with PD-L1 expression, with ORRs of 30.1% and 32.1% in patients with PD-L1-positive (n = 83) and PD-L1-negative tumors (n = 78), respectively. Overall, 199 (97.1%) patients experienced treatment-related adverse events (TRAEs), of whom 88 (42.9%) had grade ≥3 in severity. Most common Grade ≥3 TRAEs (incidence ≥10%) included lymphocyte count decreased (n = 47, 22.9%), white blood cell count decreased (n = 27, 13.2%), anemia (n = 25, 12.2%), and neutrophil count decreased (n = 23, 11.2%). TRAEs led to treatment discontinuation in 17 (8.3%) patients. Conclusions: HLX43 exhibited promising efficacy in patients with heavily pretreated advanced NSCLC, regardless of histology subtypes, and PD-L1 expression, along with manageable tolerability. Further investigation is warranted. Clinical trial information: NCT06115642 (HLX43-FIH101-phase 1 study), NCT06907615 (HLX43-NSCLC201- phase 2 study).