NEW YORK – Natera announced Thursday that it has enrolled the first participants in a clinical trial to evaluate the use of its Signatera circulating tumor DNA (ctDNA) test in guiding personalized adjuvant therapy decisions for patients with colon cancer.
The Phase III SAGITTARIUS trial aims to enroll between 700 and 900 stage III and high-risk stage II colon cancer patients who have undergone surgical resection. It is sponsored by the AIRC Institute of Molecular Oncology (IFOM-ETS) and funded by the European Union Horizon Europe Programme.
The trial is examining whether therapy based on tumor genetics and liquid biopsy improves outcomes and quality of life for high-risk stage II and stage III colon cancer patients compared to conventional therapy. The primary endpoint of the study is disease recurrence after two years in ctDNA-positive patients, and secondary endpoints consist of disease recurrence and overall survival at three and five years, with measurements of treatment safety and tolerability, Signatera testing accuracy, and patient quality of life.
Study participants will be randomized into standard or personalized treatment groups based on Signatera results. The ctDNA test gauges molecular residual disease in previously treated patients.
Signatera-positive patients will be randomized to receive either therapy tailored to their individual tumor mutational profile or six months of standard chemotherapy. Patients receiving personalized care will be given either immunotherapy or targeted agents. This genomically driven approach will focus on mismatch repair status, POLE, RAS/RAF mutation status, and HER2 amplification status.
Signatera-negative participants, meanwhile, will be randomized to receive either physician's choice of chemotherapy or observation with a shift to treatment should a positive liquid biopsy result appear. Investigators will compare treatment choices, and patients will be assessed for the possibility of de-escalation to observation or treatment with single-agent capecitabine for six months.
The trial is part of the wider SAGITTARIUS project, also funded by the European Union Horizon Europe Programme. The project focuses on health cost and quality-of-life research to assess the cost-effectiveness of interventional liquid biopsies. It also aims to pave the way for more effective tailored treatments to improve outcomes and quality of life for colon cancer patients, while potentially lowering the cost impact on private and public health systems and reducing treatment disparities. The SAGITTARIUS project consists of nine partners throughout Italy, Spain, Germany, Belgium, and Estonia.
"The trial aims to move beyond the traditional one-size-fits-all, post-surgical standard of care with chemotherapy by introducing a truly personalized treatment approach tailored to each patient," Adham Jurdi, senior medical director of oncology at Natera, said in a statement.
Earlier this year, Natera reported findings from the GALAXY arm of the CIRCULATE-Japan study that showed ctDNA status accurately predicted the risk of colorectal cancer recurrence and identified patients most likely to benefit from adjuvant therapy.
The Austin, Texas-based company is also using Signatera to guide treatment decisions in a Phase II trial in gastroesophageal cancer.