Blood-Based Colorectal Cancer Test Shows High Sensitivity in APLs

A blood-based colorectal cancer (CRC) screening test, SimpleScreen™, has shown a significant leap in performance, demonstrating high sensitivity for both malignant and advanced precancerous lesions (APL). ¹ Data from a large-scale validation study will be presented at the ASCO Gastrointestinal Cancers Symposium.

In the head-to-head validation study of 966 average-risk samples, the updated SimpleScreen assay achieved a CRC sensitivity of 85% and an APL sensitivity of 22%, both at a 90% specificity.

The performance gains were attributed to a comprehensive optimization of assay reagents, automated workflows, and a refined signal-to-noise ratio. By utilizing a case-control design where all patients were evaluated by both the initial and updated versions, investigators were able to isolate the impact of technical upgrades from biological cohort variations.

Notable improvements in the updated assay include:

• Limit of Detection (LoD): A 2.6-fold reduction in LoD, allowing for the identification of lower concentrations of tumor-derived signals.
• High-grade dysplasia: Sensitivity for APLs with high-grade dysplasia reached 44%.
• Clinical Modeling: Projections suggest the improved test version could lead to a 9% reduction in lifetime CRC cases and a 10% reduction in CRC deaths compared to previous benchmarks.

“The results [we are] presenting at ASCO GI this week for an updated CRC screening test – utilizing our personalized multi-cancer detection platform – demonstrate that we can deliver a versioning strategy to generate significant improvements in test performance,” said Aaron Elliott, PhD, CEO of SimpleScreen developer Freenome, in a news release. “As we look ahead to 2026 and the planned launch of multiple blood-based cancer screening tests, we are confident in our potential to systematically improve the detection of cancer at its earliest, most treatable stages.”

Mechanism of Action

The SimpleScreen test leverages Freenome’s proprietary platform, which integrates artificial intelligence and machine learning (AI/ML) to analyze genomic, epigenomic, and proteomic biomarkers. The current iteration specifically focuses on detecting methylation signatures in tumor-derived cell-free DNA at single-base resolution.

While current improvements are largely hardware- and reagent-based, the company indicated that future updates will focus on the underlying AI/ML algorithms to further sharpen diagnostic accuracy.

FDA Actions

Freenome is pursuing a phased regulatory strategy for the SimpleScreen platform. The initial version of the test is currently under premarket approval (PMA) review by the FDA, following submission in August 2025.

The company plans to submit a supplemental PMA for the updated, higher-performing version in 2026. This submission is expected to follow the formal approval of the first-generation test and will be supported by data from a larger, independent clinical validation study.

If approved, the rollout would mark a pivotal moment in the liquid biopsy landscape, offering a noninvasive alternative to traditional screening methods with the potential to improve patient adherence and early intervention outcomes.

PREEMPT CRC Study

The increased clinical sensitivity is higher than previously reported in the PREEMPT CRC (NCT04369053)² study. This was a prospective, multi-center, observational study to validate the blood-based test for early detection of CRC.

REFERENCES

1.Freenome delivers improved performance in its colorectal cancer blood test with sensitivity of 85% for CRC and 22% for advanced precancerous lesions. Freenome. News release. January 6, 2026. Accessed January 8, 2026. https://tinyurl.com/2k832j9v

2.Prevention of colorectal cancer through multiomics blood testing (PREEMPT CRC). ClinicalTrials.gov. Updated December 26, 2025. Accessed January 8, 2026. https://clinicaltrials.gov/study/NCT04369053