A phase 1 trial of OMO-103, a MYC inhibitor, in advanced solid tumors evaluated safety, tolerability, pharmacokinetics, and preliminary antitumor activity. The study enrolled 22 patients across six dose levels (DLs), with treatment continuing until disease progression. The most common adverse events were grade 1 infusion-related reactions, occurring in ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, with tissue saturation signs at DL5 and a terminal half-life of 40 hours in serum. Of the 19 patients evaluable for response, 12 reached the 9-week time point for assessment of drug antitumor activity, with eight showing stable disease by CT. One patient showed a 49% reduction in total tumor volume. Transcriptomic analysis supported target engagement in tumor biopsies, and soluble factors were identified as potential pharmacodynamic and predictive response markers. The recommended phase 2 dose was determined as DL5 (6.48 mg/kg). The drug showed safety and tolerability across all DLs, with no maximum tolerated dose reached. Antitumor activity was observed in some patients, with one showing 8% tumor shrinkage and another showing a 49% reduction in tumor volume. Target engagement was confirmed through transcriptomic analysis, with shutdown of MYC transcriptional signatures in patient biopsies. Predictive and pharmacodynamic biomarkers were identified, including soluble factors associated with immune response. The study demonstrated that OMO-103 is a promising MYC inhibitor with potential for further clinical development.A phase 1 trial of OMO-103, a MYC inhibitor, in advanced solid tumors evaluated safety, tolerability, pharmacokinetics, and preliminary antitumor activity. The study enrolled 22 patients across six dose levels (DLs), with treatment continuing until disease progression. The most common adverse events were grade 1 infusion-related reactions, occurring in ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, with tissue saturation signs at DL5 and a terminal half-life of 40 hours in serum. Of the 19 patients evaluable for response, 12 reached the 9-week time point for assessment of drug antitumor activity, with eight showing stable disease by CT. One patient showed a 49% reduction in total tumor volume. Transcriptomic analysis supported target engagement in tumor biopsies, and soluble factors were identified as potential pharmacodynamic and predictive response markers. The recommended phase 2 dose was determined as DL5 (6.48 mg/kg). The drug showed safety and tolerability across all DLs, with no maximum tolerated dose reached. Antitumor activity was observed in some patients, with one showing 8% tumor shrinkage and another showing a 49% reduction in tumor volume. Target engagement was confirmed through transcriptomic analysis, with shutdown of MYC transcriptional signatures in patient biopsies. Predictive and pharmacodynamic biomarkers were identified, including soluble factors associated with immune response. The study demonstrated that OMO-103 is a promising MYC inhibitor with potential for further clinical development.