eligibility_summary
Inclusion: Unresectable/metastatic urothelial carcinoma, ≤2 prior lines (chemo then avelumab=1, (neo)adjuvant with relapse ≤12 mo counts), measurable disease (RECIST 1.1), ECOG 0–1, adequate hematology (plt ≥100k, ANC ≥1500 no growth factor 14 d, Hgb ≥9 no EPO/RBC 14 d), only one prior ADC. Exclusion: uncontrolled illness/other active cancers, brain mets unless stable ≥4 wk and steroids off/stable ≥14 d, meningitis, major GI bleeding, malabsorption, or GI surgery/tubes, other per protocol.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06424717 (withdrawn before enrollment) planned a single‑arm Phase 2 of avelumab plus tuvusertib in advanced urothelial carcinoma after progression on prior anti‑PD-(L)1 therapy. Interventions and mechanisms: • Avelumab: human IgG1 monoclonal antibody immune checkpoint inhibitor targeting PD‑L1. Mechanism: blocks PD‑L1 interaction with PD‑1/B7.1 to restore cytotoxic T‑cell activity, Fc can mediate ADCC. • Tuvusertib (M1774): oral small‑molecule ATR kinase inhibitor. Mechanism: inhibits ATR‑CHK1 DNA damage response/replication stress checkpoint, promoting tumor cell death and potentially increasing tumor immunogenicity. Cells/pathways targeted: • PD‑1/PD‑L1 axis on tumor and immune cells to reactivate effector T cells. • ATR‑mediated DDR pathway in tumor cells (replication stress/S‑phase checkpoint). Combination aims to overcome resistance to prior PD‑(L)1 therapy by coupling DDR inhibition with immune reactivation.