Abstract 3435: Identification of potential biomarkers of response to OMO-103, a first-in-modality pan-MYC inhibitor, in patients with advanced solid tumors
Authors: Beaulieu Marie-Eve , Garralda Elena , Casacuberta-Serra Sílvia , Martínez-Martín Sandra Sandra , Calvo Emiliano , Moreno Víctor , López-Estévez Sergio , Foradada Laia , Alonso Guzman , Corral Elena , Doger Bernard , Hernández Tatiana , Grueso Judit , González-Larreategui Íñigo Íñigo , Pozo Erika Serrano del , Thabussot Hugo , Cano Virginia Castillo , Zacarías-Fluck Mariano F. Mariano F. , Kaur Jastrinjan , Giuntini Fabio , Whitfield Jonathan R. , Morales Josefa , Niewel Manuela , Soucek Laura 
Published: April 2023

Abstract
Background: MYC is a key transcription factor driving and maintaining human tumors. Since MYC has long been perceived as an “undruggable” target, to date, there is still no MYC inhibitor approved for clinical use. However, we designed and validated Omomyc, a MYC dominant negative mini-protein, demonstrating its potent therapeutic impact in various mouse models of cancer. Importantly, a Phase 1 study testing OMO-103, an Omomyc-based mini-protein developed by Peptomyc S.L., was successfully completed in 2022. Here, we present the main findings of the study and associated biomarker program.
Material and Methods: A phase I dose escalation study was performed in all-comers solid tumor patients, with a 3+3 design of 6 dose levels ranging from 0.48 to 9.72mg/kg, as a weekly 30-min i.v. infusion. Tumor and liquid biopsies were collected at screening, upon and at the end of treatment, to assess different biomarkers of drug activity.
Results: 22 patients with advanced solid tumors were included and 18 patients were considered evaluable for response by CT scan. Of these, 9 achieved SD. The PK analysis revealed a plasma half-life of &gt;40h. No ADAs were detected in any of the patients. Drug pharmacodynamics supported target engagement, as demonstrated by Digital Spatial Profiling analysis showing shut down of MYC transcriptional signature in patients’ tumor biopsies. In addition, a distinctive pharmacodynamic cytokine signature that correlated with stable disease was found through liquid biopsies already 3 to 4 weeks before CT scan. Importantly, a cytokine signature was also identified as being predictive of disease stabilization at baseline and could help stratify patients in upcoming additional clinical studies. Finally, several anti-tumor immune related markers were also found modulated upon OMO-103 treatment.
Conclusion: OMO-103 demonstrates a favorable safety profile, with encouraging signs of activity supported by predictive and pharmacodynamic biomarkers worthy of further investigation.
Citation Format: Marie-Eve Beaulieu, Elena Garralda, Sílvia Casacuberta-Serra, Sandra Sandra Martínez-Martín, Emiliano Calvo, Víctor Moreno, Sergio López-Estévez, Laia Foradada, Guzman Alonso, Elena Corral, Bernard Doger, Tatiana Hernández, Judit Grueso, Íñigo Íñigo González-Larreategui, Erika Serrano del Pozo, Hugo Thabussot, Virginia Castillo Cano, Mariano F. Mariano F. Zacarías-Fluck, Jastrinjan Kaur, Fabio Giuntini, Jonathan R. Whitfield, Josefa Morales, Manuela Niewel, Laura Soucek. Identification of potential biomarkers of response to OMO-103, a first-in-modality pan-MYC inhibitor, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3435.