563P - Preliminary analysis in Protector-C study: A prospective, multicenter cohort of utilizing circulating tumor DNA (ctDNA) methylation as postoperative surveillance for colorectal cancer (CRC)

Background

The detection of minimal residual disease (MRD) post-surgery in CRC is aiding in the early recurrence detection and timely intervention to improve patient survivals. Our previous proof-of-concept study (clinical trial#NCT03737539) demonstrated the efficiency of ctDNA methylation in MRD detection and its significance as a risk factor for recurrence. To validate these findings in real-world, we initiated Protector-C study, a large prospective, multicenter cohort aimed at recruiting postoperative CRC pts over a 2-year surveillance period. Here, we present preliminary results of the baseline and correlation of ctDNA dynamics with outcomes in pts.

Methods

The Protector-C cohort aims to prospectively enroll pts with stage I-IV primary CRC from seven centers. ColonAiQ® test, was chosen to trace ctDNA dynamics in serial plasma samples collected before surgery, 1, and once every 3 months post-surgery until recurrence or 24th moth. Standard clinical procedure was followed. The primary endpoint was disease-free survival (DFS), defined as the time between surgery and detection of relapse/death for any cause.

Results

Until March 2024, 322 pts were enrolled and analyzed in this preliminary study. The median follow-up was 11.77 months, and 17 pts experienced relapse. Before surgery, 244 pts (75.8%) were positive with ctDNA methylation (termed as ctDNA+), while only 99 (30.7%) positive for carcinoembryonic antigen (CEA). At one month after surgery (POM1), a significant decrease (25.8%) in ctDNA+ was observed, indicating ctDNA methylation was sensitive to detect the changes of tumor burden. Even within a relatively short surveillance period, we have observed that ctDNA+ pts exhibited a significantly inferior DFS compared to ctDNA- pts (p<0.001). Notably, 12 of 17 relapse pts were ctDNA+ at POM1, and only 5 pts among 239 ctDNA- pts relapsed within a year.

Conclusions

Based on preliminary analysis, ColonAiQ®-based ctDNA methylation enables sensitive MRD detection and serves as a significant prognostic risk factor in CRC. The ongoing Protector-C study will establish the postoperative utility of ColonAiQ® test for ctDNA-guided surveillance strategies in CRC.

Clinical trial identification

NCT05444491.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Singlera Genomics (China) LTD., Yangzhou, China.

Disclosure

Y. Zhang: Financial Interests, Institutional, Full or part-time Employment: Singlera Genomics. H. Jia: Financial Interests, Institutional, Full or part-time Employment: Singlera Genomics. H. Wang: Financial Interests, Institutional, Full or part-time Employment: Singlera Genomics. R. Liu: Financial Interests, Institutional, Full or part-time Employment: Singlera Genomics. All other authors have declared no conflicts of interest.