Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study

Area of Science:

• Oncology
• Genomics
• Clinical Trials

Background:

• Circulating tumor DNA (ctDNA) analysis offers a minimally invasive approach for genomic profiling.
• Routine implementation of ctDNA in phase I clinical trials is not yet established.
• Molecular Tumor Boards (MTBs) require timely genomic data for patient stratification.

Purpose of the Study:

• To evaluate the feasibility and utility of ctDNA-based genomic profiling in a phase I clinical trials setting.
• To assess the concordance of ctDNA analysis with matched tumor tissue.
• To determine the turnaround time for ctDNA results and their impact on clinical decision-making.

Main Methods:

• The TARGET program utilized a 641-gene panel for ctDNA analysis, assessing both somatic mutations and copy number alterations (CNA).
• ctDNA was analyzed from blood samples of 100 patients with advanced cancers.
• Actionable mutations were identified using a 2.5% variant allele frequency (VAF) threshold.

Main Results:

• ctDNA analysis demonstrated good concordance with matched tumor tissue.
• Actionable mutations were identified in 41% (41 of 100) of patients.
• 11 patients received matched therapy based on ctDNA findings, with results available within a clinically acceptable timeframe for MTB review.

Conclusions:

• ctDNA-based genomic profiling is a feasible and valuable tool for patient stratification in early-phase clinical trials.
• This approach enhances the identification of patients eligible for targeted therapies.
• The study provides a practical framework for integrating routine blood-based genomic analysis into clinical practice.