Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, has unveiled groundbreaking new data from the Phase III CALGB (Alliance) / SWOG 80702 study. These findings were presented as a late-breaking oral presentation on January 25, 2025, at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, CA. This study represents a significant milestone in the field of personalized medicine for colorectal cancer (CRC), focusing on the utility of the Signatera test to guide adjuvant treatment decisions.
The CALGB (Alliance) / SWOG 80702 trial is the first study of its kind to evaluate whether patients identified as Signatera-positive after surgery benefit from an escalation in adjuvant therapy. Specifically, the study assessed the addition of celecoxib, a widely available non-steroidal anti-inflammatory drug (NSAID), to the standard adjuvant chemotherapy regimen of FOLFOX in stage III CRC patients. The pre-specified analysis involved approximately 1,000 patients, all of whom had available post-surgical plasma samples and were randomized to receive FOLFOX with or without celecoxib.
Key Findings from the Study
Signatera-Positive Patients
Signatera-positivity, determined through post-surgical plasma testing, was predictive of significant improvements in disease-free survival (DFS) and overall survival (OS) with the addition of celecoxib to the standard adjuvant FOLFOX regimen. Among Signatera-positive patients, the inclusion of celecoxib led to a marked improvement in three-year DFS, increasing it to 44.1% compared to 26.6% in the placebo group. The hazard ratio (HR) for DFS was 0.55 (95% CI 0.39-0.80; p=0.001), indicating a substantial reduction in the risk of disease recurrence. Similar benefits were observed for overall survival, with an HR of 0.58 (95% CI 0.38-0.90; p=0.013).
Signatera-Negative Patients
In contrast, no survival benefit was observed with the addition of celecoxib in Signatera-negative patients, highlighting the specificity of the Signatera test in identifying those who would benefit from treatment escalation.
Predictive Value of Signatera
Signatera status after surgery and prior to the initiation of adjuvant therapy was highly predictive of disease recurrence. Patients who were Signatera-positive showed significantly worse outcomes in both DFS (HR 7.14, 95% CI: 5.54-9.21; p<0.0001) and OS (HR 6.72, 95% CI: 4.91-9.18; p<0.0001) compared to their Signatera-negative counterparts.
Implications for Personalized Medicine
“The results from the CALGB (Alliance) / SWOG 80702 study mark an unprecedented moment in personalized medicine for patients with colorectal cancer,” said Alexey Aleshin, M.D., corporate chief medical officer and general manager of oncology for Natera. “We demonstrated Signatera’s ability to predict a benefit in both disease-free survival and overall survival for Signatera-positive patients from the addition of celecoxib, an extremely accessible, affordable, and well-tolerated therapy. These data also offer compelling evidence to address an unmet need in adjuvant colorectal cancer treatment, where there has not been a new drug approval in over 20 years.”
The findings emphasize the importance of molecular residual disease (MRD) testing with Sig as a tool to personalize treatment plans, ensuring that patients most at risk of recurrence receive additional therapeutic interventions while avoiding unnecessary treatment in others.
Insights from the ALTAIR Trial
In addition to the CALGB (Alliance) / SWOG 80702 study, results from the randomized, double-blind ALTAIR clinical trial were also presented at ASCO GI. The ALTAIR trial investigated treatment escalation with Trifluridine/Tipiracil (FTD/TPI) in patients with stage I-IV colorectal cancer who were -positive. The trial included 243 patients randomized to receive either FTD/TPI or a placebo over six months.
Results in All Patients
While the ALTAIR trial demonstrated a trend toward improved DFS in the FTD/TPI group, with a median DFS of 9.3 months compared to 5.6 months in the placebo group, the results did not reach statistical significance (HR, 0.79; p=0.107). However, these findings still suggest potential clinical benefits of FTD/TPI for certain subgroups.
Results in Resected Oligometastatic Stage IV Patients
A notable and statistically significant benefit was observed in resected oligometastatic stage IV patients treated with FTD/TPI. In this subgroup, the median DFS was 9.76 months in the treatment group compared to 3.96 months in the placebo group (HR, 0.53; p=0.012). These results highlight an important opportunity for treatment escalation in stage IV patients who test positive for MRD.
Broader Implications for Colorectal Cancer Treatment
The combined results from the CALGB (Alliance) / SWOG 80702 and ALTAIR trials underscore the critical role of MRD testing in advancing the field of colorectal cancer treatment. By identifying patients who are most likely to benefit from additional therapies, Signatera enables a more tailored approach to care, improving outcomes while minimizing unnecessary toxicity and costs.
Moreover, the use of an affordable and well-tolerated drug like celecoxib in Signatera-positive patients could address a longstanding gap in adjuvant colorectal cancer treatment, where new drug approvals have been scarce. Similarly, the promising findings from the ALTAIR trial suggest that targeted treatment escalation could provide meaningful benefits for select patient populations, such as those with resected oligometastatic stage IV disease.
About Signatera
Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer, and muscle-invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. has been clinically validated across multiple cancer types and indications, with published evidence in over 100 peer-reviewed papers.
About Natera
it is a global leader in cell-free DNA and genetic testing, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard of care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. ’s tests are validated by more than 250 peer-reviewed publications that demonstrate high accuracy. operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California. For more information, visit www.natera.com.
