MATRiX: A randomized phase II trial of tuvusertib (ATR inhibitor) with or without avelumab in advanced anti-PD(L)-1 refractory Merkel cell carcinoma
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 50 participants or records.
Read the paper
Related studies
- Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38
- Anti-influenza virus activity of green tea by-products in vitro and efficacy against influenza virus infection in chickens
- Therapeutic Potential of Mesenchymal Stem Cells (MSCs) and MSC-Derived Extracellular Vesicles for the Treatment of Spinal Cord Injury
- The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model
- Enhanced anticancer efficacy of TRAIL-conjugated and odanacatib-loaded PLGA nanoparticles in TRAIL resistant cancer
- In vivo tracking of bioorthogonally labeled T-cells for predicting therapeutic efficacy of adoptive T-cell therapy
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.