HLX43 (anti–PD-L1 ADC) drives 31% ORR in heavily pretreated NSCLC—PD-L1–independent activity

HLX43 is an antibody–drug conjugate (ADC) targeting PD-L1, evaluated in pooled NSCLC cohorts from the Phase 1 HLX43-FIH101 dose escalation/expansion and the global Phase 2 HLX43-NSCLC201 dose exploration/expansion studies (NCT06115642; NCT06907615), with heavily pretreated patients (median 2 prior lines; range 1–9) treated Q3W at 0.5–4.0mg/kg (pooled treated n=205; response-evaluable n=161). Investigator-assessed ORR was 31.1% overall, including 36.4% in squamous NSCLC at 2.0mg/kg (n=33) and 47.4%/50.0% in nonsquamous EGFR-wildtype (n=19)/EGFR-mutant (n=16) at 2.5mg/kg; responses were similar in PD-L1–positive vs PD-L1–negative tumors (30.1% vs 32.1%), which compares favorably to historical post-platinum docetaxel monotherapy ORRs typically in the ~10% range and to atezolizumab vs docetaxel where ORR was ~14% vs 13% in OAK (cross-trial, acknowledging different eras/eligibility). TRAEs occurred in 97.1% with grade ≥3 TRAEs in 42.9%—notably cytopenias (grade ≥3 lymphocyte decrease 22.9%, WBC decrease 13.2%, anemia 12.2%, neutrophil decrease 11.2%)—and discontinuation due to TRAEs was 8.3%, a toxicity profile that looks more “ADC-like” (myelosuppression) than the checkpoint-inhibitor SOC options in similar lines.