eligibility_summary
Inclusion: Adults 18–75 with advanced/metastatic solid tumors lacking standard options, ≥1 measurable lesion, ECOG 0–1, life >3 mo, recovery to ≤G1, washouts (≥28 d major therapy, ≥14 d targeted/hormone/TCM/minor), tumor tissue for PD‑L1/DDX5, adequate organs, HCC Child‑Pugh A, contraception/negative pregnancy. Exclusion: recent other cancers, ≥G3 irAEs, ILD, severe mAb allergy, active infection (TB/HBV/HCV), HIV/immunodef/transplant, major CV/CNS disease or uncontrolled CNS mets, active autoimmune (except hypothyroid/T1DM), recent steroids/immunosuppressants, strong CYP2D6/3A use, live vaccine, pregnancy/lactation, investigator judgment.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: First‑in‑human Phase I of HLX43 in advanced/metastatic solid tumors. Intervention: HLX43, an anti–PD‑L1 antibody–drug conjugate (ADC), IV Q3W, the monoclonal antibody targets PD‑L1 and is conjugated (DAR ~8) to a high‑potency DNA topoisomerase I inhibitor. Mechanisms of action: (1) Immune checkpoint blockade—binding PD‑L1 blocks the PD‑1/PD‑L1 axis, restoring T‑cell antitumor activity, (2) Targeted cytotoxicity—after PD‑L1–mediated internalization, the topo‑I payload is released to cause DNA damage, replication stress, and apoptosis in PD‑L1+ cells. Cells/pathways targeted: PD‑L1–expressing tumor cells and immunosuppressive cells in the tumor microenvironment, PD‑1/PD‑L1 immune checkpoint and DNA replication/repair via topoisomerase I. PD‑L1 and DDX5 expression may be explored as biomarkers.