Foresight Diagnostics showcased the improved sensitivity and superior clinical performance of MRD detection by Foresight CLARITY in early-stage NSCLC within the post-operative adjuvant setting as compared to MRD detection by conventional liquid biopsy-based methods.

Foresight CLARITY MRD detection platform is powered by PhasED-Seq, a technology that utilizes a patient’s unique set of phased variants to identify circulating tumor DNA (ctDNA) as a measure of residual disease. Research shows that over 50% of NSCLC patients harbor ctDNA levels below 1 part per ten thousand, which is the typical limit of detection of conventional MRD assays. By leveraging its proprietary phased variant technology, Foresight CLARITY delivers an analytical sensitivity of less than 1 part per million

Key Highlights:

• >2x improved detection: In pre-treatment samples, Foresight CLARITY accurately detected ctDNA MRD in 62% (13 of 21 cases) of early-stage (I and II) lung adenocarcinomas compared to a detection rate of only 29% (6 of 21 cases) by conventional SNV-based methods.  

• >2x improved clinical sensitivity: Foresight CLARITY detected MRD at the post-therapy landmark in 67% of patients (12 out of 18 cases) who relapsed compared to conventional SNV-based methods only detecting MRD in 28% (5 out of 18 cases). 

• Superior clinical performance in an adjuvant setting: Retrospective analysis of this cohort using Foresight CLARITY showed that post-operative ctDNA MRD positive patients that received adjuvant therapy demonstrated significantly improved outcomes and achieved MRD clearance compared to ctDNA MRD positive patients that did not receive therapy (see figures below). Among postoperative ctDNA MRD-negative patients, no significant difference in outcomes was observed between those who did and did not receive adjuvant therapy.  

Conclusion

The study concluded that ultrasensitive detection of ctDNA was achieved using PhasED-Seq technology, with MRD detected at levels below 1 ppm. This translated to improved clinical sensitivity of MRD at key landmarks in early-stage NSCLC compared to current SNV-based detection assays. PhasED-Seq predicted the benefit of adjuvant therapy, such that there was no observed therapeutic benefit in the MRD-- population, but there was a benefit observed in the MRD+ population. Together, these data suggest that ultrasensitive MRD detection is promising for use in risk-adapted trials in early-stage NSCLC.