Clinical Utility of ctDNA in Detecting Resistance Mechanisms and Delivering Precision Medicine to Cancer Patients

Inclusion Criteria All cohorts: * Age ≥18 years old * Ability to provide written informed consent * Presence of metastatic or unresectable disease * Being reviewed and treated through medical oncology service at Royal Marsden Hospital Cohort 1: Locally Advanced/Metastatic NSCLC * Oncogene-addicted NSCLC (i.e. ESCAT Tier 1 oncogenic drivers: EGFR/ALK/ROS1/RET/MET/BRAF/NTRK/HER2/KRAS), AND * Progressive disease on targeted therapy (any line) within the 6 weeks prior to consent Cohort 2: Locally Advanced/Metastatic GIST * Locally advanced/metastatic gastrointestinal stromal tumour (GIST), AND * Progressive disease on targeted therapy (any line) within the 6 weeks prior to consent Cohort 3: Metastatic Colorectal Cancer • Metastatic colorectal cancer, left sided, RAS wild type, HER2 any status, AND * If HER2 negative or unknown: progressive disease on systemic anti-cancer therapy (SACT) with an anti-EGFR agent (e.g. cetuximab) within the 6 weeks prior to consent * If HER2 positive: progressive disease on first line systemic anti-cancer therapy (SACT) +/- an anti-EGFR agent within the 6 weeks prior to consent Cohort 4: Locally Advanced/Metastatic BTC * Identified targetable mutation (IDH1 mutation/HER2 amplification/FGFR2 fusion or rearrangement/NTRK fusion/BRAF V600E mutation/MMR deficiency \[dMMR\]), AND * Progressive disease on targeted therapy (any line) demonstrated within the 6 weeks prior to consent Cohort 5: Advanced/Metastatic ovarian cancer * Diagnosis of advanced/metastatic high-grade ovarian cancer, AND * Known BRCA status, AND * Progressive disease on a PARP-inhibitor (with or without bevacizumab) following platinum-based therapy in the 1st line maintenance setting, within the 6 weeks prior to consent Exclusion Criteria All cohorts: * Medically unstable to commit to sampling required for the study * ECOG performance status ≥3