Natera and Incyte Collaborate on MRD-Guided Colorectal Cancer Treatment Study

The trial will investigate whether circulating tumor DNA (ctDNA) testing can identify patients at elevated risk of recurrence who may benefit from additional treatment before disease becomes detectable through imaging.

The NEXERA-204 study will evaluate INCA33890, Incyte’s investigational bispecific immunotherapy, in patients with stage II or III microsatellite-stable colorectal cancer who have undergone surgery and completed adjuvant chemotherapy. The study is designed to assess the potential of treating patients with molecular evidence of residual cancer following standard therapy, even when no disease is visible on imaging.

Following chemotherapy, patients will undergo longitudinal monitoring with Natera’s Signatera test for up to 12 months. Those who test MRD-positive but show no radiographic evidence of disease may qualify for enrollment and treatment with INCA33890. This approach aims to identify patients who remain at increased risk of recurrence despite completing treatment intended to cure their cancer.

Signatera is a personalized, tumor-informed blood test that analyzes ctDNA to detect molecular residual disease and monitor recurrence risk. The assay uses genetic alterations identified in an individual patient’s tumor to track tumor-derived DNA in the bloodstream. In the new study, Signatera will be incorporated into both primary and secondary endpoints to evaluate molecular response to treatment.

INCA33890 is an investigational bispecific antibody targeting programmed cell death protein 1 (PD-1) and transforming growth factor-beta receptor 2 (TGFβR2). The therapy is designed to modulate immune signaling pathways involved in tumor growth and immune suppression. Its potential to improve outcomes in patients with persistent MRD after colorectal cancer treatment remains under investigation.

Natera contributed clinical and real-world evidence, along with expertise in MRD-guided trial design, to support development of the study. The company will also provide clinical trial-matching services to identify eligible patients based on Signatera results and other enrollment criteria. The collaboration is part of a broader effort to evaluate treatment strategies guided by molecular evidence of residual cancer.

The study follows a treatment-on-MRD (TOMR) approach, in which molecular testing is used to identify patients for intervention before radiographic progression. By incorporating serial ctDNA measurements into patient selection and treatment evaluation, researchers aim to determine whether earlier intervention can improve outcomes in patients at increased risk of colorectal cancer recurrence.

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