Fast-TRACKing precision oncology for rare cancers: A national decentralized trial offering comprehensive genomic profiling and a molecular tumor board.

Abstract

3147 Background: The TargetCancer Foundation TCF-001 TRACK study (Target RAre Cancer Knowledge, NCT04504604) initiated on Oct 01, 2020, is a fully remote, advocacy-driven decentralized precision trial seeking to evaluate the clinical impact of utilizing comprehensive genomic profiling (CGP) reviewed by a molecular tumor board (MTB) for patients (pts) with rare cancers. Methods: Pts were remotely enrolled/consented. Blood samples were collected via mobile phlebotomy and tested with FoundationOne Liquid CDx; tissue biopsies (TBx) were tested using FoundationOne CDx ± laboratory developed (LD) FoundationOne RNA or LD FoundationOne Heme. Liquid biopsy testing (LBx) included algorithmic predictions for clonal hematopoiesis (CH). MTB reviewed results and provided recommendations. Results: As of Oct 01, 2025, 230 pts from 46 US states were enrolled with evaluable results; 76% (175/230) had TBx and LBx, 22% LBx, and 2% TBx biopsies. MTB review was completed for 226 pts. Median age was 57 years (interquartile range [IQR]: 47,66); > 60 tumor types were represented: cholangiocarcinoma (35%), gastrointestinal (19%), soft tissue-related sarcomas (17%), brain (14%), and others (15%). First on-study TBx CGP (n=173) showed microsatellite instability high in 2%, homologous repair deficiency-signature in 2%, and median tumor mutational burden (TMB) of 1.3 mut/Mb (IQR: 0.8,3.6; 5 pts ≥ 10 mut/Mb). In LBx (n=57), ctDNA tumor fraction (TF) was ≥1% in 28% of pts; median blood TMB was 1.3 (IQR: 0,2.5; 1 pt ≥ 10 mut/Mb). Overall, 95% (219/230) of tumors had >1 pathogenic alteration; TBx CGP detected alterations in 96% (172/179), most frequently TP53 (35%), CDKN2A (29%), CDKN2B (21%), KRAS (19%), MTAP (17%), and TERT (14%). LBx CGP detected alterations in 85% (192/225), with tumor-derived (TD) variants in KRAS (11%), IDH1 (7%), and CDKN2A (6%). TP53 (31%) included both TD and CH variants, while DNM3TA (30%), ATM (10%), TET2 (10%), and CHEK2 (8%) were mostly CH. In brain tumors, 52 variants from 28 pts with LBx identified 45 CH, 4 germline, and 3 TD. Across all tumor types, 9% (20/230) had biomarkers for FDA-approved tissue-agnostic therapies. This includes ERBB2 amplification (2% overall), which is often correlated with HER2 immunohistochemistry positivity. LBx sensitivity for DNA tissue-detected clonal SVs and rearrangements was 85% (95% CI: 0.74,0.92) when ctDNA TF≥1%; 24% (95% CI: 0.19,0.29) when <1%. Pathogenic fusions detected by RNA sequencing were not detected by DNA in 33% of cases (9/27). Conclusions: CGP identified pathogenic alterations in nearly all rare cancer patients, with tissue-agnostic biomarkers in 9%. RNA sequencing adds diagnostic yield. CH in liquid biopsies underscores need for expert MTB interpretation. TRACK, a first-of-its-kind national decentralized trial, provides a scalable framework for equitable precision oncology access. Clinical trial information: NCT04504604 .