What question did this study set out to answer?

This research aims to assess the clinical impact of comprehensive genomic profiling for patients with rare cancers.

May 29, 2026

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

Key Points

This research aims to assess the clinical impact of comprehensive genomic profiling for patients with rare cancers.
Patients were remotely enrolled and consented.
Blood samples were collected via mobile phlebotomy and analyzed using FoundationOne Liquid CDx and FoundationOne CDx.
Molecular tumor board reviewed genomic alterations to guide clinical recommendations.
95% of enrolled patients had at least one pathogenic alteration detected.
Tissue biopsies identified alterations in 96% of cases, commonly TP53 and CDKN2A.
9% of patients had biomarkers for tissue-agnostic therapies, indicating potential treatment options.

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 .

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