Nature Medicine.

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

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. Nature Medicine (2024).

Abstract.

Among the ‘most wanted’ targets in cancer therapy is the oncogene MYC, which coordinates key transcriptional programs in tumor development and maintenance. It has, however, long been considered undruggable. OMO-103 is a MYC inhibitor consisting of a 91-amino acid miniprotein. Here we present results from a phase 1 study of OMO-103 in advanced solid tumors, established to examine safety and tolerability as primary outcomes and pharmacokinetics, recommended phase 2 dose 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 six 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 ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, with tissue saturation signs at DL5 and a terminal half-life in serum of 40 h. Of the 19 patients evaluable for response, 12 reached the predefined 9-week time point for assessment of drug antitumor activity, eight of those showing stable disease by computed tomography. One patient defined as stable disease by response evaluation criteria in solid tumors showed a 49% reduction in total tumor volume at best response. Transcriptomic analysis supported target engagement in tumor 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−1).

ClinicalTrials.gov identifier: NCT04808362.
doi: https://doi.org/10.1038/s41591-024-02805-1

Results.

Most interestingly, subjecting the Luminex data to QLattice technology enabled us to identify a distinct signature predictive of disease stabilization in response to OMO-103 and independent of oncological indication or previous treatment. Such a signature encompasses four of the soluble factors identified as significantly lower at baseline for patients with SD. These factors generate three independent models of prediction (Fig. 5c) that include the combination of two soluble markers. Again, ROC curve analysis suggested that these three combination models are outstanding predictors of SD outcome and that their predictive power is improved compared with that of their individual models (CD62E + MIP-1β, AUC = 0.96; MCP-1 + MIP-1β, AUC = 0.98; CD62E + IL-8, AUC = 0.98; Extended Data Fig. 3b).

Try the QLattice.

Experience the future of AI, where accuracy meets simplicity and explainability.

Models developed by the QLattice have unparalleled accuracy, even with very little data, and are uniquely simple to understand.

The QLattice: Explainable AI

Share this publication.

The QLattice accelerates discoveries with explainable insights.​

Researchers and and scientists cite Abzu’s QLattice symbolic AI in industry-leading journals for introducing a new standard of performance and explainability to data sets.

Subscribe for
notifications from Abzu.

You can opt out at any time. We’re cookieless, and our privacy policy is actually easy to read.