The study evaluates the safety, tolerability, and preliminary efficacy of OMO-103, a MYC inhibitor, in advanced solid tumors. OMO-103 is a 91-amino acid miniprotein derived from Omomyc, a MYC dominant-negative protein. The phase 1 trial used a 3 + 3 design with six dose levels, enrolling 22 patients. The most common adverse events were grade 1 infusion-related reactions, and one dose-limiting toxicity occurred at the highest dose level (DL5). Pharmacokinetic analysis showed nonlinearity and tissue saturation at DL5, with a terminal half-life of 40 hours in serum. Of the 19 evaluable patients, eight showed stable disease by CT scan, and one patient showed a 49% reduction in total tumor volume. Transcriptomic analysis confirmed 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\(^{-1}\)). The study highlights the safety and preliminary efficacy of OMO-103, suggesting further investigation in specific indications.The study evaluates the safety, tolerability, and preliminary efficacy of OMO-103, a MYC inhibitor, in advanced solid tumors. OMO-103 is a 91-amino acid miniprotein derived from Omomyc, a MYC dominant-negative protein. The phase 1 trial used a 3 + 3 design with six dose levels, enrolling 22 patients. The most common adverse events were grade 1 infusion-related reactions, and one dose-limiting toxicity occurred at the highest dose level (DL5). Pharmacokinetic analysis showed nonlinearity and tissue saturation at DL5, with a terminal half-life of 40 hours in serum. Of the 19 evaluable patients, eight showed stable disease by CT scan, and one patient showed a 49% reduction in total tumor volume. Transcriptomic analysis confirmed 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\(^{-1}\)). The study highlights the safety and preliminary efficacy of OMO-103, suggesting further investigation in specific indications.