WCLC 2025 - Posters & ePosters-PT2.10.03 Safety, Tolerability and Preliminary Efficacy of Anti-PD-L1 ADC HLX43 in Advanced/Metastatic Solid Tumors: A Phase I Study

PT2.10.03 Safety, Tolerability and Preliminary Efficacy of Anti-PD-L1 ADC HLX43 in Advanced/Metastatic Solid Tumors: A Phase I Study

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This open-label, first-in-human phase 1 trial (NCT06115642) assessed the safety, pharmacokinetics, and preliminary efficacy of HLX43, a novel PD-L1-targeting antibody-drug conjugate (ADC), in 56 patients with advanced or metastatic non-small cell lung cancer (NSCLC) refractory to standard therapies. HLX43 consists of a high-affinity PD-L1 antibody linked to a potent topoisomerase 1 inhibitor payload via a stable, tumor microenvironment-activated tripeptide linker.<br /><br />Patients received HLX43 intravenously every three weeks at doses of 2.0 mg/kg and 2.5 mg/kg during phase 1a and 1b dose escalation and expansion cohorts. The median follow-up was 9.0 months. Tumor imaging was conducted regularly to evaluate response per RECIST v1.1.<br /><br />Investigator-assessed objective response rate (ORR) among 54 evaluable patients was 37.0%, with a disease control rate (DCR) of 87.0%. Subgroup analysis showed ORR of 28.6% in squamous NSCLC and 46.2% in non-squamous NSCLC. Notably, patients with EGFR wildtype non-squamous NSCLC had a confirmed ORR of 46.7%, rising to 60.0% at the 2.5 mg/kg dose. Patients with brain metastases had an ORR of 36.4% and a DCR of 100%. Tumor shrinkage up to 100% was observed in patients experiencing immune-mediated lung disease, an immune-related adverse event reported in 14.3% of patients.<br /><br />Treatment-related adverse events (TRAEs) occurred in all patients, with 46.4% experiencing grade 3 TRAEs. The most common severe events were anemia (19.6%), white blood cell count decrease (19.6%), neutropenia (16.1%), and lymphopenia (12.5%). Immune-related AEs occurred in 21.4%, mainly lung inflammation, generally manageable.<br /><br />HLX43 showed promising efficacy and manageable safety in heavily pretreated NSCLC patients regardless of molecular subtype or prior therapy, including those with brain metastases. These results support further clinical development of HLX43 as a potential new treatment option for advanced NSCLC patients who have failed standard therapies.

Asset Subtitle

Jie Wang

Meta Tag

Speaker Jie Wang

Topic Metastatic Non-small Cell Lung Cancer – Cytotoxic Therapy

Keywords

HLX43

PD-L1 antibody-drug conjugate

non-small cell lung cancer

phase 1 clinical trial

objective response rate

disease control rate

topoisomerase 1 inhibitor

immune-related adverse events

brain metastases

dose escalation