Natera announces new data from GALAXY arm of ongoing CIRCULATE-Japan trial

Natera announced that new data from the GALAXY arm of the ongoing CIRCULATE-Japan trial was released today at the 2024 Congress of the European Society for Medical Oncology in Barcelona, Spain. GALAXY is one of the largest and most comprehensive prospective studies of circulating tumor DNA testing in resectable colorectal cancer. This latest analysis, which will also be published in Nature Medicine on September 16, provides the first evidence of the ability of Signatera-based molecular residual disease detection to predict overall survival. The data also demonstrates Signatera’s ability to predict adjuvant chemotherapy benefit in resectable CRC, with ctDNA clearance as an indicator of a superior survival benefit compared to no clearance. In the study, 2,240 patients with stage II-IV CRC were monitored using Signatera after curative-intent surgery with a median follow-up of 23 months. Key takeaways include: Signatera status was predictive of overall survival. Signatera-positivity in the post-op MRD window was found to be significantly associated with worse OS compared to Signatera-negative patients with a 36-month OS of 71.80% vs. 96.0%, respectively. This 10x advantage in overall survival compares favorably to all known guideline-recommended biomarkers that have HRs for overall survival in a range of 1-4. Signatera status was predictive of an overall survival benefit from adjuvant chemotherapy. High-risk stage II and stage III-IV patients who were Signatera-positive after surgery and received ACT demonstrated superior OS, corresponding to a 50% reduction in the risk of death when treated with ACT. By comparison, the MOSAIC trial1, which was the last practice-changing study in adjuvant CRC, demonstrated a 16% reduction in risk of death. Signatera-negative patients did not derive an OS benefit from ACT. Signatera status remained the most significant predictor of recurrence. Signatera-positivity after surgery was the single most significant prognostic factor associated with inferior DFS and OS in a multivariate analysis that included all clinicopathologic risk factors currently in use. This is also reflected by the 36-month DFS difference between Signatera-positive and Signatera-negative patients at 16.7% versus 83.5%, respectively. The association of Signatera-positivity with a significantly increased risk for recurrence was observed across all pathologic stages. Sustained Signatera clearance after ACT was associated with improved survival. Patients who clear ctDNA and remained Signatera-negative had superior survival benefit with 24-month OS of 100%. This compares to patients who cleared ctDNA for a period of time but later become Signatera-positive, with 24-month OS of 82%, and patients who did not achieve ctDNA clearance, with 24-month OS of 61%. This finding further supports the utility of sustained ctDNA clearance as a surrogate endpoint for long-term outcomes.