MYC targeting by OMO-103 in solid tumors: a phase 1 trial

Among the most-wanted targets in cancer therapy is the oncogene MYC, a pleiotropic transcription factor coordinating programs in tumor development and maintenance, yet long considered undruggable. OMO-103 is a 91–amino acid MYC-inhibitory miniprotein. We report results from a first-in-human phase 1 study of OMO-103 in advanced solid tumors. Primary endpoints were safety and tolerability; secondary endpoints included pharmacokinetics (PK), recommended phase 2 dose (RP2D) and preliminary activity. Using a classical 3 + 3 design, patients received weekly intravenous single-agent OMO-103 in 21-day cycles across six dose levels (DLs). Twenty-two patients were enrolled and treated until progression. The most common adverse events were grade 1 infusion-related reactions (IRRs) in ten patients; one dose-limiting toxicity occurred at DL5. PK showed nonlinearity with tissue saturation at DL5 and a terminal serum half-life of ~40 h. Of 19 response-evaluable patients, 12 reached the 9-week assessment; eight achieved stable disease by CT. One patient with stable disease by RECIST had a 49% reduction in total tumor volume at best response. Transcriptomics supported target engagement in tumor biopsies. We identified soluble factors as potential pharmacodynamic and predictive markers. The RP2D was determined as DL5 (6.48 mg/kg). ClinicalTrials.gov: NCT04808362.

Elena Garralda, Marie-Eve Beaulieu, Víctor Moreno, Sílvia Casacuberta-Serra, Sandra Martínez-Martín, Laia Foradada, Guzman Alonso, Daniel Massó-Vallés, Sergio López-Estévez, Toni Jauset, Elena Corral de la Fuente, Bernard Doger, Tatiana Hernández, Raquel Perez-Lopez, Oriol Arqués, Virginia Castillo Cano, Josefa Morales, Jonathan R. Whitfield, Manuela Niewel, Laura Soucek, Emiliano Calvo