Analysis of 1,000+ patients, with 12 months mean follow up, demonstrates clinical utility of Signatera for informing post-surgical treatment decisions

 Natera, Inc. (NASDAQ: NTRA), a leader in personalized genetic testing and diagnostics, today announced new data recently presented on the clinical utility of Signatera, its personalized and tumor-informed molecular residual disease (MRD) test, at the American Society of Clinical Oncology's 2022 Gastrointestinal Cancers Symposium (ASCO GI). The oral presentation included an updated analysis from the landmark CIRCULATE-Japan trial analyzing a cohort of colorectal cancer (CRC) patients.

More than 3,000 CRC patients are now enrolled in CIRCULATE-Japan, the largest prospective, multi-center, MRD-guided trial in CRC, using Signatera to monitor MRD status in patients with stage I-IV CRC up to 96 weeks post-surgery. The latest analysis of more than 1,000 patients from the observational GALAXY arm of the study highlighted three novel findings that were presented at the conference:

• Signatera positivity is predictive of treatment benefit: patients who were MRD-positive at 4 weeks post-op benefited significantly from adjuvant chemotherapy (ACT), across all stages of disease.
• Signatera-negative patients did not benefit from ACT: patients with high-risk stage II and stage III disease who were MRD-negative at 4 weeks post-op did not derive significant benefit from ACT (p-value of .63).
• Signatera dynamics during ACT is predictive of treatment benefit: 68% of ACT-treated patients cumulatively cleared their ctDNA by week 24 and had significantly better outcomes relative to those who remained ctDNA-positive, with a hazard ratio of 15.8.

In addition, the single time point post-surgical sensitivity of Signatera in stage II and III CRC was 67.6%. This sensitivity analysis included over 5 times more cancer recurrences than previously reported in Reinert, et. al.¹

"Definitive evidence has now been presented that personalized MRD testing can guide adjuvant treatment decisions, particularly for MRD-positive patients who clearly benefit from adjuvant chemotherapy," said the CIRCULATE-Japan study's principal investigator, Dr. Takayuki Yoshino, of the National Cancer Center Hospital East, Kashiwa, Chiba, Japan. "We see these results as an important step forward in establishing MRD-guided adjuvant therapy as the standard of care for colorectal cancer patients worldwide."

"Current guidelines recommend combination chemotherapy for all patients with stage III CRC, yet it is known that up to 40% are cured by surgery alone. Our study demonstrates that MRD testing can help stratify and predict which patients are likely to benefit from systemic therapy," said Alexey Aleshin, M.D., VP of oncology medical affairs at Natera. "We are extremely pleased with these groundbreaking results from CIRCULATE-Japan and are optimistic they may change practice guidelines."

The full presentation, as shown at ASCO GI, is available here.