eligibility_summary
Eligibility: Adults ≥18 with untreated advanced/metastatic non-squamous NSCLC, PD-L1 TPS <50% (22C3 central), measurable disease (RECIST v1.1), consented/compliant, provide tumor tissue for TROP2/biomarkers. Adjuvant/neoadjuvant allowed if ≥6 mo pre-metastatic and no early progression. Exclude: prior topoisomerase-I ADC, TROP2 therapy, any ICI, live vaccine ≤30 days, active/untreated CNS mets, major cardiac disease, severe pulmonary compromise/pneumonectomy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3 randomized first-line study in advanced/metastatic non‑squamous NSCLC (PD‑L1 TPS <50%, no actionable alterations). Arms: (a) datopotamab deruxtecan (Dato‑DXd) + pembrolizumab + platinum, (b) Dato‑DXd + pembrolizumab, (c) pembrolizumab + pemetrexed + platinum. Dato‑DXd: TROP2‑directed antibody‑drug conjugate delivering the topoisomerase I inhibitor DXd, binds TROP2 on tumor cells, is internalized, releases payload to induce DNA damage/cell death (bystander effect possible). Pembrolizumab: anti‑PD‑1 monoclonal antibody immune checkpoint inhibitor restoring T‑cell activity by blocking PD‑1/PD‑L1 signaling. Pemetrexed: antifolate antimetabolite inhibiting TS/DHFR/GARFT, depleting nucleotide synthesis. Carboplatin/cisplatin: platinum DNA‑crosslinking agents. Targets/pathways: TROP2 on tumor cells, Topo‑I/DNA replication, PD‑1 on T cells, folate‑dependent nucleotide synthesis, DNA damage response.