e21205 Background: Solid tumor molecular testing has advanced our ability to identify an increasing number of targetable genomic alterations (alts). As the number of alts with matched therapies multiplies, tissue biopsy material can be quickly exhausted, resulting in multiple undergenotyped patients (pts). Non-invasive cell-free circulating tumor DNA (cfDNA) assays can detect all National Comprehensive Cancer Network (NCCN) recommended somatic genomic alts, improving treatment and derived costs on health systems. Methods: Adult pts presenting to a Colombian hospital system with stage IV non-small cell lung cancer (NSCLC) or other metastatic solid malignancies (stage III-IV), with tissue unavailable for biopsy or insufficient quantity (QNS) to perform genotype studies in 1st line or progressive disease, documented QNS for genotyping studies by pathology report or negative report, clinical refractoriness to chemotherapy suspected to be related to a genetic alt, or not willing to undergo biopsy or invasive tests were prospectively recruited. Pts underwent clinical cfDNA analysis utilizing a next generation sequencing assay that evaluates single nucleotide variants, and select indels, fusions, and copy number amplifications in up to 73 genes (Guardant360). Clinical outcomes were correlated with cfDNA results. Results: 21 pts met inclusion criteria and underwent cfDNA testing. In 81% (N = 17), at least one genomic alt was found. 29.4% of pts had an alt associated with an FDA approved therapy (N = 5), 88.2% had an alt associated with an off-label therapy or ongoing clinical trial (N = 15), and 29.4% (N = 5) had an alt associated with therapeutic resistance. For all pts with an alt associated with an FDA approved therapy, treatment redirectioning was decided. Given the difficulties in our health system, no off-label therapy has been authorized and no pts who had alts related to clinical trials have been enrolled in one. Conclusions: Almost one-third of pts with cfDNA detected had a genomic alt associated with an FDA approved therapy resulting in a therapy change. In this cohort of pts from Colombia, cfDNA testing provided therapeutically actionable information and avoided repeat invasive biopsies.