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Soo Park, MD
Soo Park, MD
Posted: Monday, June 15, 2026
Merkel cell carcinoma (MCC) is characterized by defects in G1 checkpoint control, rapid proliferation, and dependence on S/G2 checkpoint pathways, including ATR (ataxia telangiectasia mutated and Rad3-related). Patients with advanced MCC who experience disease progression after anti–PD-L1 therapy have few effective treatment options and generally poor outcomes. Preclinical evidence suggests ATR inhibition can enhance immunogenic cell death, providing a rationale for combining ATR-targeted therapy with immune checkpoint blockade. The MATRiX study (NCT05947500), a multicenter, National Cancer Institute–sponsored phase II trial, evaluated tuvusertib (an ATR inhibitor) either as monotherapy or in combination with avelumab in patients with anti–PD-L1–refractory MCC. The results of the study were presented at the 2026 ASCO Annual Meeting (Abstract LBA9514).
Study Details
Between May 2024 and September 2025, 35 patients were randomly assigned to receive tuvusertib alone (180 mg on days 1–14 of a 21-day cycle; n = 10) or tuvusertib plus avelumab (1,600 mg every 21 days; n = 25). One patient was later deemed ineligible and excluded from all analyses. The median age was 73 years. More than half of the patients (53%) had primary immune checkpoint inhibitor (ICI)–refractory disease, and 65% had received at least two prior systemic therapies. Patients whose disease progressed on monotherapy were permitted to cross over to the combination arm. The primary endpoint of the trial was progression-free survival.
Key Results
The monotherapy arm met prespecified futility criteria after no objective responses were observed among the first 10 treated patients and was subsequently closed. In addition, none of the four patients who crossed over from monotherapy to the combination arm achieved an objective response.
By contrast, the combination of tuvusertib and avelumab produced one complete response and four partial responses, yielding an overall response rate of 20.8% (95% confidence interval = 7.1%–42.2%). Responses were observed in both primary and acquired ICI-resistant disease, including four patients with primary resistance. Four of the five responders remained progression-free at the January 2026 data cutoff, with ongoing responses ranging from 182 to 273 days after treatment initiation; the fifth patient experienced disease progression after 479 days. One-year progression-free survival estimates were 26.4% for the combination arm compared with 0% for monotherapy. One-year overall survival estimates were 36.5% and 29.2%, respectively.
Grade 3 or higher treatment-emergent adverse events occurred in 58% of patients receiving the combination and 80% of those receiving monotherapy. The most common toxicities included lymphopenia, anemia, and fatigue. According to the investigators, the safety profile was consistent with prior experience with these agents.
The investigators concluded: “Tuvusertib with avelumab demonstrated antitumor activity in anti-PD-(L)1-refractory MCC, inducing durable clinical benefit in ICI-resistant metastatic [patients] with limited salvage options. No signal of anticancer efficacy was observed with ATR [inhibitor] monotherapy. These findings warrant further investigation of ATR [inhibition] in combination with immunotherapy in ICI-refractory MCC.”
DISCLOSURE: The study was funded by the EDDOP Leadership Award-P30. For full disclosures of the study authors, visit coi.asco.org.
2026 ASCO Annual Meeting (Abstract LBA9514)
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