Data from MONETTE: A Randomized Phase II Study of Ceralasertib plus Durvalumab or Ceralasertib Monotherapy in Patients with Advanced Melanoma Resistant to PD-(L)1 Inhibition

作者：Max Schlaak, Carolina Cimminiello, Jacopo Pigozzo, Jeeyun Lee, Stephan Grabbe, Piotr Rutkowski, Jacek Mackiewicz, Katy K. Tsai, Paolo A. Ascierto, Mario Mandalà, Fabrizio Carnevale‐Schianca, Sebastian Haferkamp, Victoria Atkinson, Jessica C. Hassel, Shahneen Sandhu, William H. Sharfman, Emma Dean, Urwah Noor, Sonia Iyer, Roy Rabbie, Antoni Ribas · 年份：2026 · DOI：10.1158/1078-0432.c.8600801 · 研究领域：Medicine、Internal medicine、Oncology、Urology、Gastroenterology、Surgery

<div>AbstractPurpose:Data suggest that ceralasertib, a potent and selective oral inhibitor of the ataxia-telangiectasia and Rad3-related (ATR) DNA damage response kinase, may overcome resistance to prior immunotherapy.Patients and Methods:In this phase II study, patients with unresectable or metastatic melanoma of cutaneous, acral, or mucosal subtype and confirmed progression during anti–PD-(L)1 therapy with or without anti–CTLA-4 were randomized 2:1 to ceralasertib 240 mg twice daily on days 1 to 7 and then durvalumab 1,500 mg intravenously on day 8, every 28 days or ceralasertib 240 mg twice daily on days 1 to 7, every 28 days. The primary endpoint was objective response rate (ORR). Key secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses of baseline (tumor and circulating) and on-treatment (circulating only) biomarkers were conducted.Results:ORR was 9.3% [95% confidence interval (CI), 4.3–16.9] for ceralasertib plus durvalumab (below the prespecified minimum threshold) and 5.8% (95% CI, 1.2–15.9) for ceralasertib monotherapy; median PFS was 2.0 months (95% CI, 1.9–3.5) versus 1.9 months [95% CI, 1.9–3.1; hazard ratio (HR), 0.80; 95% CI, 0.54–1.18]; and median OS was 16.0 months [95% CI, 10.5–not calculated (NC)] versus 12.3 months (95% CI, 9.5–NC; HR, 0.81; 95% CI, 0.49–1.37). Both regimens were well tolerated. Exploratory analyses indicated a possible link...