Triple DDR Assault: ART0380 and Low-Dose Irinotecan Yield High Responses in ATM-Negative Tumors

In this first-in-human study, advanced cancer patients received ART0380 (ATR inhibitor) with low-dose irinotecan, with the recommended phase 2 dose established at 200mg ART0380 on days 1-3 and 8-10 and irinotecan at 60mg/m² on days 1 and 8 of a 21-day cycle. The regimen was well-tolerated and demonstrated promising clinical efficacy, particularly in ATM-negative cancers where a 45% confirmed RECIST response rate was observed across a variety of tumor types.

Enhanced activity in ATM-deficient tumors underscores the potential of combining ATR inhibition with chemotherapy to exploit replication stress vulnerabilities, paving the way for biomarker-driven treatment strategies in advanced solid tumors.