eligibility_summary
Adults 18–75 with ECOG 0–1, advanced/metastatic NSCLC, central lab–confirmed functional HER2 mutation, no prior systemic therapy for advanced disease, ≥1 extracranial measurable lesion (RECIST v1.1), and adequate organ function. Exclude small-cell/sarcomatoid mix, other targetable drivers, active/untreated CNS or leptomeningeal mets, uncontrolled pain, other malignancies, ILD/pneumonitis, autoimmune disease, severe cardiovascular disease, or active HBV/HCV.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: Phase III, first-line in advanced/metastatic HER2‑mutated NSCLC. Interventions and mechanisms: • SHR-A1811 (experimental): HER2-targeted antibody–drug conjugate (ADC). Binds HER2 on tumor cells, is internalized, and releases a topoisomerase I–inhibitor payload, causing DNA damage and tumor cell death (potential bystander effect). • Standard of care (comparator): Camrelizumab (anti–PD‑1 IgG4 monoclonal antibody) plus investigator’s choice chemotherapy—pemetrexed (antifolate antimetabolite inhibiting thymidylate synthase, DHFR, GARFT), or paclitaxel (taxane microtubule stabilizer), with carboplatin or cisplatin (platinum DNA crosslinkers). Targeted cells/pathways: • HER2‑mutant NSCLC cells and HER2 pathway, topoisomerase I–mediated DNA replication. • T cells via PD‑1/PD‑L1 immune checkpoint. • Tumor cell nucleotide synthesis (folate-dependent enzymes), microtubule dynamics, and DNA crosslink–induced apoptosis.