eligibility_summary
Eligible: adults (≥18) with unresectable/metastatic Merkel cell carcinoma, RECIST-evaluable, progressed on anti–PD-(L)1 (last dose ≥14 d, PD on chemo if used), ECOG ≤2, adequate marrow/renal/hepatic function, treated/stable brain mets, controlled HIV/HBV/HCV allowed, contraception required. Exclude: severe prior irAEs, ataxia telangiectasia, pregnancy, QTcF>470 ms, PPIs, strong CYP3A4/1A2/MATE drugs, inability to swallow, uncontrolled illness, other trials, >10 mg steroids. Crossover: Arm 1 PD with labs.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05947500 (MATRiX) is a randomized phase 2 study in advanced, PD-(L)1–refractory Merkel cell carcinoma comparing tuvusertib alone vs tuvusertib + avelumab. Tuvusertib (M1774) is an oral small‑molecule ATR kinase inhibitor that blocks the ATR–CHK1 DNA damage response/replication‑stress pathway, impairing DNA repair, stalling tumor replication, and inducing tumor cell death. Avelumab (Bavencio) is an anti‑PD‑L1 IgG1 monoclonal antibody (immune checkpoint inhibitor) that blocks PD‑1/PD‑L1 signaling to restore cytotoxic T‑cell activity and can mediate ADCC. Targets: tumor cells with high replication stress/NE features, ATR/DDR pathway, PD‑L1 on tumor and immune cells, effector T cells (checkpoint relief) and NK cells (ADCC). Primary aim: determine if adding PD‑L1 blockade to ATR inhibition improves progression‑free survival and response.