eligibility_summary
Measurable R/M HNSCC (oropharynx, oral cavity, hypopharynx, larynx, not nasopharynx), incurable by local therapy, no prior systemic therapy for R/M (prior CRT >4 mo allowed), ECOG 0–1, PD-L1–positive, recent tumor tissue (biopsy/resection, no cytology or bone), HPV status if oropharyngeal. Exclude prior checkpoint inhibitors, other malignancy unless CR ≥2y/no therapy, high bleeding risk, PD ≤4 mo post-curative, LM or uncontrolled/symptomatic CNS mets, active autoimmune on immunosuppression.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2, first-line platform in PD-L1+ recurrent/metastatic HNSCC testing: dostarlimab (anti–PD-1 IgG4 mAb) alone vs combinations with belrestotug (anti-TIGIT Fc-enabled IgG1), nelistotug (anti-CD96 mAb), remzistotug (anti-CD112R/PVRIG mAb), and a triple (dostarlimab+belrestotug+nelistotug). Mechanisms: dostarlimab blocks PD-1/PD-L1 to reinvigorate exhausted T cells, belrestotug blocks TIGIT and can deplete TIGIT+ Tregs via Fc, enhancing CD226 co-stimulation, nelistotug blocks CD96 to relieve PVR/CD155-mediated inhibition, remzistotug blocks CD112R to counter NECTIN-2 inhibition. Targets: CD8+ T cells, Tregs, and NK cells via PD-1 and the DNAM-1 (CD226)/PVR–NECTIN checkpoint axis.