Clinical validation of the Northstar Response: A novel quantitative methylation ctDNA monitoring assay for advanced GI cancer treatment response.

• DOI: 10.1200/jco.2025.43.4_suppl.839
• Publication Date: 2025-01-27T14:35:52Z
• Authors: Ilyas Sahin; Derek Li; Doga Kahramangil; Abdul Qahar K. Ya...; Lee D McDaniel; Maegan Cremer; George P. Kim; Sherise C. Rogers; Brian Hemendra Ra...; Meghan Ferrall-Fa...; Ji-Hyun Lee; Thomas J. George

839 Background: Circulating tumor DNA (ctDNA) is a promising tool for monitoring treatment response but challenged by pan-cancer quantification and consistent outcome correlations. Northstar Response (NSR) quantifies >500 cancer specific methylated loci, offering reflection of disease burden clinical response. Methods: We present prospective observational study to evaluate the utility NSR. Patients with advanced GI cancers had serial ctDNA assessed at baseline during systemic correlations radiographic or Tumor methylation scores (TMS) were expressed as Log10 values mixed-effects model evaluated assessment Results: 73 patients locally metastatic analyzed. Among these, 35 (47.9%) least four assays all assessments. The median age was 66 years (± 8.5), most being male (67.1%) White (74.0%). Table 1 shows case distribution. Baseline TMS significant variation (p=0.023), measurable across types. CRC exhibited highest mean TMS-log10 while biliary pancreatic lowest. Cases both primary lesions higher than cases either tumors alone (3.4 vs. 3.0). Compared stable responsive disease, changes correlated progressive coefficient 0.48 third collection time point (p=0.05). However, 23/73 (32%) without an on-treatment timepoint (OTT) due rapid progression (average death 24 103 days OTT). In exploratory modeling relative RECIST-like those OTT, NSR evaluations associated assessments (p<0.04, Fisher’s Exact Test). Conclusions: consistently varied types burden. appeared when accounting progressors. Additional analyses are ongoing will be presented. cohort characteristics. Characteristic HCCN = 25 (34%) BTC N 12 (16%) EGAN CRCN 11 (15%) PDACN 8 (11%) Other 5 (7%) p-value Age Median (25% 75%) 67 (63 - 76) 68.5 (62.3 – 75.5) 73.5 (62.5 75.3) 54 (39.5 60) 67.5 (55.5 76.3) 60 (57 63) 0.008 3.2 (2.3 3.9) 2.5 (2.1 3.4) (2.2 3.8) 4.4 (3.5 5) (1.9 3.3) 4 5.2) 0.023 Primary (48%) (66.7%) (100%) 6 (54.5%) 7 (87.5%) (80%) 0.015 First line therapy not 23 (92%) (41.7%) 3 (37.5%) 0.001 Progressive 16 (64%) (33.3%) 9 (75%) (45.5%) 0.2 Death 13 (52%) (25%) (63.6%) 2 (40%) Kruskal-Wallis rank sum test; exact test.