Natera Inc. has announced the enrollment of the first patients in the SAGITTARIUS clinical trial, a global, randomized, phase III study designed to evaluate the use of Signatera in guiding personalized adjuvant treatment strategies for patients with colon cancer. The trial, sponsored by The AIRC Institute of Molecular Oncology (IFOM-ETS) and funded by the European Union Horizon Europe Programme, aims to enroll approximately 700-900 stage III and high-risk stage II colon cancer patients following surgical resection.
Personalized Treatment Approach
The SAGITTARIUS trial is designed to move beyond the traditional one-size-fits-all, post-surgical standard of care with chemotherapy. Signatera-positive patients will be randomized to receive either genotype-guided therapy tailored to their individual tumor mutational profile or six months of standard chemotherapy. The trial’s investigational arm will explore the potential of administering immunotherapy or targeted agents approved for metastatic colon cancer earlier in the disease course to increase the proportion of patients cured with adjuvant therapy. This genomically-driven approach will focus on mismatch repair status, POLE, RAS/RAF mutation status, and HER2 amplification status.
For Signatera-negative patients, the trial will compare physician choice treatments with options for de-escalation to observation or single-agent capecitabine for six months.
Collaborative Effort
The SAGITTARIUS trial includes collaborations with 9 partners in 5 countries in Europe, and a network of 26 clinical centers in Italy, Spain, and Germany. According to Silvia Marsoni, MD, PhD, head of the precision oncology unit at IFOM ETS and scientific coordinator of the SAGITTARIUS Project, the enrollment of the first patients in SAGITTARIUS represents a significant milestone in a trial that has the potential to transform treatment approaches for colorectal cancer.
Signatera's Role
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. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in over 100 peer-reviewed papers.
Potential Impact
The SAGITTARIUS project also includes health cost and quality of life research to comprehensively assess the full cost-effectiveness of interventional liquid biopsy. The project aims to pave the way for more effective, tailored treatments that enhance both 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. Adham Jurdi, MD, senior medical director of oncology at Natera, stated that the trial aims to introduce a truly personalized treatment approach tailored to each patient and that they are optimistic that the study will generate evidence to support the de-escalation of chemotherapy for Signatera-negative patients.
Clara Montagut, MD, PhD, head of the gastrointestinal cancer unit at Hospital del Mar in Barcelona, Spain, and principal investigator of the SAGITTARIUS clinical trial, emphasized the study’s innovative goals, noting that they aim to anticipate the use of therapies tailored to the molecular landscape of the patient’s tumor, including immunotherapy and targeted therapies with proven efficacy in the metastatic setting within the adjuvant treatment context.
