First Prospective GALAXY Study Data on Colorectal Cancer Released at ESMO; Shows Signatera Predicts Survival

Natera, Inc. (NASDAQ: NTRA), a global leader in genetic testing, revealed fresh data from the GALAXY segment of the ongoing CIRCULATE-Japan trial during the 2024 Congress of the European Society for Medical Oncology (ESMO) in Barcelona, Spain. The GALAXY trial stands as one of the most extensive and thorough studies on circulating tumor DNA (ctDNA) testing in treatable colorectal cancer (CRC).

The newly released data, also set to be published in Nature Medicine on September 16, present groundbreaking evidence on the capability of Signatera's molecular residual disease (MRD) detection to predict overall survival (OS). The study further demonstrates Signatera’s potential to forecast the benefits of adjuvant chemotherapy (ACT) in treatable CRC, with the clearance of ctDNA serving as an indicator of a better survival outcome than no clearance.

The study observed 2,240 patients with stage II–IV CRC post-curative surgery, with a median follow-up of 23 months. Key findings from the study are as follows:

1. Signatera status was predictive of overall survival. Patients who tested positive for Signatera in the post-operative MRD window had significantly worse overall survival compared to those who tested negative (HR: 9.68, p-value < 0.01), with a 36-month OS of 71.80% versus 96.0%, respectively. This 10-fold survival advantage is superior to all current guideline-recommended biomarkers, whose HRs for overall survival range from 1 to 4.

2. Signatera status was predictive of an overall survival benefit from ACT. High-risk stage II and stage III-IV patients who tested positive for Signatera after surgery and received ACT exhibited better overall survival (adjusted HR: 0.53, p-value = 0.05), reflecting a 50% reduction in the risk of death when treated with ACT. In comparison, the MOSAIC trial showed a 16% reduction in death risk (HR: 0.84, p-value = 0.05).

3. Signatera-negative patients did not derive an overall survival benefit from ACT (adjusted HR: 0.53, p-value = 0.13).

4. Signatera status remained the most significant predictor of recurrence. Post-surgery Signatera positivity was the most critical prognostic factor associated with poorer disease-free survival (DFS) (HR 12.08, p-value < 0.01) and OS (HR 9.87, p-value < 0.01), as per a multivariate analysis that included all current clinicopathologic risk factors. This is evidenced by the 36-month DFS difference between Signatera-positive and negative patients at 16.7% (95% CI: 12.1–21.9%) versus 83.5% (95% CI: 81.2%–85.6%), respectively. The significantly increased recurrence risk associated with Signatera positivity was observed across all pathologic stages.

5. Sustained Signatera clearance after ACT was linked to improved survival. Patients who cleared ctDNA and remained Signatera-negative, referred to as “sustained clearance,” had a superior survival benefit with a 24-month OS of 100%. This contrasts with patients who experienced “transient clearance” of ctDNA, with a 24-month OS of 82%, and those who did not achieve ctDNA clearance, with a 24-month OS of 61%. These findings support the utility of sustained ctDNA clearance as a surrogate endpoint for long-term outcomes.

Dr. Yoshiaki Nakamura, a co-author of the paper and principal investigator from the National Cancer Center Hospital East in Kashiwa, Chiba, Japan, commented, “We now have compelling prospective evidence from a large trial of more than 2,200 patients that clearly reinforces the link between MRD status and overall survival.” He added that these findings suggest that Signatera can predict post-surgical outcomes for colorectal cancer patients with high precision, aiming to significantly improve patient outcomes by redefining the future of personalized medicine.

Dr. Minetta Liu, chief medical officer of oncology at Natera, stated, “The GALAXY data released today builds on an earlier analysis from the same study published in Nature Medicine in 2023. Introducing 36-month, first-of-its-kind data on overall survival is an important milestone that reinforces the potential to improve outcomes for patients diagnosed with colorectal cancer. The updated data affirms ctDNA status as a critical measure both for prognosis and for predicting which patients may truly benefit from adjuvant chemotherapy.”

Signatera is a personalized, tumor-informed molecular residual disease test for previously diagnosed cancer patients. It utilizes ctDNA to detect and quantify residual cancer, identify recurrence earlier than standard tools, and help optimize treatment decisions. The test is available for clinical and research use, covered by Medicare for colorectal, breast, ovarian cancers, and muscle-invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with evidence published in over 70 peer-reviewed papers.

Natera™ is a global leader in cell-free DNA and genetic testing dedicated to oncology, women’s health, and organ health. The company aims to make personalized genetic testing and diagnostics standard care to protect health and inform earlier, more targeted interventions leading to longer, healthier lives. Natera's tests are validated by more than 200 peer-reviewed publications, demonstrating high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California.