eligibility_summary
Incl: unresectable locally advanced or metastatic NSCLC, no prior systemic therapy, fresh tumor sample, PD‑L1 high (TC ≥50%), measurable disease (RECIST v1.1), ECOG 0–1, adequate organ function. Excl: actionable EGFR/ALK/other 1L drivers, surgery <4 wks or lung RT >30 Gy <6 mo, prior ICI, never‑smoker, other invasive cancer <5 y, active CNS mets/LMD, autoimmune needing tx <2 y, live vaccine <30 d, pneumonitis/IPF, symptomatic effusions, active IBD, cardiac dz <6 mo, severe infection <4 wks/TB, prior transplant.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3, double-blind trial in first-line PD-L1–high NSCLC comparing belrestotug + dostarlimab vs placebo + pembrolizumab. Belrestotug (GSK4428859A/EOS‑448) is a Fc‑competent anti‑TIGIT monoclonal antibody (immunotherapy) that blocks the TIGIT checkpoint (ligands CD155/CD112) to enhance T‑cell and NK‑cell activity and may deplete TIGIT‑high Tregs via ADCC. Dostarlimab is an anti‑PD‑1 IgG4 monoclonal antibody that blocks PD‑1/PD‑L1 signaling to reinvigorate exhausted T cells. Pembrolizumab is also an anti‑PD‑1 IgG4 checkpoint inhibitor (active comparator). Targets/pathways: TIGIT on T cells, Tregs, and NK cells, PD‑1 on activated T cells, CD155/CD112 on tumor/APCs, PD‑L1 on tumor/immune cells. Aim: test dual TIGIT+PD‑1 blockade vs PD‑1 alone.