MATRiX: A randomized phase II trial of tuvusertib (ATR inhibitor) with or without avelumab in advanced anti-PD(L)-1 refractory Merkel cell carcinoma.

作者：Rashmi Bhakuni, Evan Hall, T Gooley, Yvonne M. Mowery, George Ansstas, Andrew S. Brohl, Melissa Burgess, Maya Dimitrova, Ling Gao, Gino K. In, Jeffrey Joseph Ishizuka, Jose Lutzky, Theresa Medina, Soo J. Park, Samuel Saibil, Ann W. Silk, Judy Murray, Steven Gore, Suzanne L. Topalian, Paul Nghiem · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.17_suppl.lba9514 · 研究领域：Polyomavirus and related diseases、Viral Infections and Outbreaks Research、Peripheral Neuropathies and Disorders

LBA9514 Background: Advanced Merkel cell carcinoma (MCC) often responds to anti-PD-(L)1, but patients (pts) with immune checkpoint inhibitor (ICI)-refractory disease have poor outcomes and few therapy options. MCC has defects in G1 checkpoint control, proliferates rapidly, and is reliant on S/G2 checkpoints such as ATR (ataxia telangiectasia mutated and Rad3-related). Inhibiting ATR can promote immunogenic cell death. MATRiX (MCC refractory to immunotherapy treated with ATR inhibitor ± avelumab) is a multicenter, NCI-sponsored, randomized, open-label phase II trial evaluating tuvusertib, an ATR inhibitor, alone (Arm 1) or in combination with avelumab (Arm 2) in anti-PD-(L)1-refractory MCC, NCT05947500. Methods: Pts were randomized 1:1 using a permuted-block design. Arm 1 received tuvusertib 180 mg PO on days 1-14 of each 21-day cycle. Arm 2 received tuvusertib as in Arm 1, plus avelumab 1600 mg IV every 21 days. Pts with disease progression in Arm 1 were eligible to cross over to Arm 2. The planned sample size (N=50; 25 per Arm) provided >80% power to observe a statistically significant (1-sided level of 0.15) difference in the primary endpoint, progression-free survival (PFS), assuming a hazard ratio of 0.5. Secondary endpoints were overall response rate (ORR), duration of response, and overall survival (OS). Data cutoff: January 20, 2026. Results: From 5/2024 to 9/2025, 35 subjects (median age 73) received therapy: Arm 1, n=10; Arm 2, n=25. One pt was deemed ineligible p...