Natera Begins Patient Enrollment for Phase III Colon Cancer Trial SAGITTARIUS

Natera, Inc., a prominent player in the field of cell-free DNA and genetic testing, has announced the commencement of patient enrollment in the SAGITTARIUS clinical trial. This trial is a landmark study in the domain of personalized adjuvant treatment strategies for colon cancer patients. Sponsored by The AIRC Institute of Molecular Oncology (IFOM-ETS) and supported by the European Union Horizon Europe Programme, the trial is a global, randomized, phase III study focused on utilizing Signatera to tailor treatments for individuals with colon cancer.

The SAGITTARIUS study targets the enrollment of 700 to 900 patients who have stage III or high-risk stage II colon cancer and have undergone surgical resection. For patients who test positive with Signatera, the trial offers two paths: they will either receive a treatment plan customized to their specific tumor mutational profile or undergo a six-month regimen of standard chemotherapy. The investigational arm of the study is particularly innovative, as it looks into the early use of immunotherapy or targeted treatments—typically reserved for metastatic colon cancer—to potentially cure more patients during the adjuvant therapy phase. This approach is deeply rooted in genomic data, focusing on markers such as mismatch repair status, POLE, RAS/RAF mutation status, and HER2 amplification.

Conversely, for patients whose Signatera results are negative, the trial provides options that could include physician-chosen treatments, observation, or a simplified treatment with single-agent capecitabine for six months. This aspect of the trial seeks to generate evidence for potentially reducing the intensity of chemotherapy in certain patients.

The SAGITTARIUS trial involves collaboration among nine partners across five European countries, with clinical centers spread across Italy, Spain, and Germany. "The beginning of patient enrollment in SAGITTARIUS marks a crucial step forward in potentially revolutionizing colorectal cancer treatment methods," stated Silvia Marsoni, MD, PhD, who is at the helm of the precision oncology unit at IFOM-ETS and oversees the scientific coordination of the SAGITTARIUS Project. The study's objective is to transition from generalized post-surgical chemotherapy to a more personalized treatment paradigm, which addresses the unique genetic makeup of each patient's cancer.

Adham Jurdi, MD, the senior medical director of oncology at Natera, highlighted the trial's potential benefits, mentioning that Signatera-positive patients will receive adjuvant therapies that precisely match their genetic profiles. Furthermore, the trial's findings could support a reduction in chemotherapy for patients who are Signatera-negative.

Principal investigator of the trial, Clara Montagut, MD, PhD, emphasized the innovative nature of this study, noting the ambition to apply therapies based on the molecular composition of the patient’s tumor. The trial stands out as it integrates therapies proven effective in metastatic settings, into adjuvant treatment strategies. Montagut remarked that SAGITTARIUS is unique in its approach within the realm of liquid biopsy research.

The SAGITTARIUS Horizon Europe project, which includes the clinical trial, is part of a broader initiative aimed at assessing the cost-effectiveness of liquid biopsies in cancer care. Funded by the European Union, this project seeks to offer more personalized treatment options that could improve outcomes, enhance life quality for colon cancer patients, and potentially reduce healthcare costs. The project involves a partnership between entities in Italy, Spain, Germany, Belgium, and Estonia.

IFOM ETS, based in Milan, Italy, is renowned for its research in cancer formation and development at a molecular level. This institute, in collaboration with the AIRC Foundation for Cancer Research, emphasizes translating research findings into clinical applications. IFOM's expertise is central to the management and sponsorship of the SAGITTARIUS trial.

Signatera is a ground-breaking test that provides a personalized approach to monitoring cancer and informing treatment decisions by analyzing circulating tumor DNA. It is clinically validated and used across various cancer types, including colorectal, breast, ovarian, and muscle-invasive bladder cancers. Natera, the company behind the test, is committed to advancing personalized genetic testing and diagnostics to improve patient outcomes.