Phase Ib Basket Expansion Trial and Alternative-Schedule Dose-Escalation Study of ATR Inhibitor Elimusertib in Advanced Solid Tumors with DNA Damage Response Defects.

This phase Ib trial evaluated the ATR inhibitor elimusertib in 143 patients with advanced cancers showing DNA damage response defects. These included gynecologic, prostate, colorectal, and breast cancers, as well as ATM loss.

The drug was mainly given at 40 mg twice daily on a 3 days on/4 days off schedule. An alternative schedule was tested for patients with ATM loss or mutations.

Key findings:

• Reversible hematologic toxicities were observed with elimusertib.
• Objective response rate was modest at 4.5%.
• Disease control rate (DCR) was achieved in 49.3% of patients, especially high in gynecologic cancers at 59.5% DCR.
• No correlation was found between ATM alterations and clinical outcomes.
• Biomarker analyses suggest early circulating tumor DNA response might predict benefit from ATR inhibition.

Further research is ongoing to find optimal predictive biomarkers and combination strategies.