Leap Therapeutics identifies DKK1 as predictive marker in cancer trial

The DeFianCe trial, which evaluated sirexatamab in combination with chemotherapy and bevacizumab, failed to meet its primary endpoint of progression-free survival in the overall intent-to-treat group. However, peer-reviewed results published in Clinical Cancer Research demonstrate that the drug's efficacy is tied directly to DKK1 levels. Patients in the upper quartile of DKK1 expression saw median overall survival move from 9.5 months in the control group to a state where the median was not yet reached in the treatment arm.

Researchers emphasize that DKK1 serves as a practical, blood-based biomarker, detectable in all study participants. Because tumoral DKK1 mRNA expression is generally low, the plasma-based measurement provides a more accurate reflection of the systemic burden relevant to colorectal cancer. These findings provide the scientific rationale for a biomarker-selected Phase 3 registrational trial, as the data suggest DKK1-high patients represent a biologically distinct group with a high unmet clinical need.