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

MYC is a ‘most wanted’ target in cancer therapy and it coordinates key transcriptional programs in tumour development and maintenance. It has, however, long been considered undruggable. OMO-103 is a MYC inhibitor consisting of a 91 amino acid mini-protein. Here we present results from a Phase 1 study of OMO-103 in advanced solid tumours, to examine safety and tolerability as primary outcomes, and pharmacokinetics, RP2D and preliminary signs of activity as secondary ones. A classical 3+3 design was used for dose escalation of weekly intravenous, single agent OMO-103 administration in 21-day cycles, encompassing 6 dose levels (DLs). A total of 22 patients were enrolled, with treatment maintained until disease progression. The most common adverse events were grade 1 infusion-related reactions occurring in 10 patients. 1 dose-limiting toxicity occurred at DL5. Pharmacokinetics showed non-linearity, with tissue saturation signs at DL5, and a terminal half-life in serum of 40 hours. Of the 19 patients evaluable for response, 12 reached the pre-defined 9-week timepoint to assess drug anti-tumour activity, and 8 of those showed stable disease by computed tomography. 1 patient defined as stable disease by RECIST showed a 49% reduction of total tumour volume at best response. Transcriptomic analysis supported target engagement in tumour biopsies. In addition, we identified soluble factors that are potential pharmacodynamic and predictive response markers. Based on all these data, the recommended Phase 2 dose was determined as DL5 (6.48 mg/kg). ClinicalTrials.gov identifier: NCT04808362.