GALAXY, a large-scale prospective observational study, monitored post-surgical ctDNA MRD status in patients with clinical stage II to IV or relapsed CRC (UMIN000039205). Tumor tissue and matched normal DNA were processed for whole-exome sequencing (WES) to identify and track patient-specific somatic single nucleotide variants (SNVs), for ctDNA detection in the associated patients’ plasma samples. Actionable biomarkers having OncoKB therapeutic levels 1-3 were explored and identified separately from the Signatera test (through WES data).

In January 2024, Natera presented an analysis from the observational arm of the prospective CIRCULATE-Japan trial, in an oral presentation at the ASCO GI’s press program. GALAXY is one of the largest and most comprehensive prospective studies of MRD testing in resectable colorectal cancer. 

Subsequently on 1st June 2024, promising new findings from the CIRCULATE-Japan GALAXY study demonstrating the prognostic and predictive utility of Signatera and actionable biomarkers in colorectal cancer were presented at the ASCO 2024 meeting. The study highlighted the importance of ctDNA-based MRD as both a prognostic and predictive tool for CRC across different actionable biomarkers. The findings suggested the potential for integration of MRD-driven targeted therapeutic strategies for CRC with specific actionable biomarkers.

 GALAXY is part of the CIRCULATE-Japan trial platform, which also includes ALTAIR, a first-of-its-kind, treat on molecular recurrence study evaluating the utility of Signatera in CRC. Natera expects to announce topline results for this Phase III randomized trial in August 2024. 

The company is also conducting another study known as CIRCULATE-France. CIRCULATE-France is complementary to the CIRCULATE-Japan and CIRCULATE-US trials. While the Japanese and the US trials evaluate the benefit of MRD-guided treatment in stage III and high-risk stage II CRC patients, the French trial is focused on stage II CRC.

KOL insights

“GALAXY is the largest MRD study to date and demonstrates a relationship between ctDNA dynamics and improved clinical outcomes, suggesting ctDNA can help identify patients more likely to benefit from ACT therapy. VEGA and ALTAIR are ongoing and will help further establish ctDNA-guided ACT strategies” – Expert Opinion.

Conclusion

To conclude, the role of biomarker-guided therapy for resectable colorectal cancer is still being defined. Circulating tumor DNA has emerged as a minimally invasive biomarker for detecting molecular residual disease and predicting recurrence. Tumor-informed ctDNA testing, with its ability to combine tumor sequencing and MRD detection in a single workflow, shows promise for facilitating integration into clinical practice.