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

Area of Science:

• Oncology
• Molecular Biology
• Drug Development

Background:

• The oncogene MYC is a critical target in cancer therapy but has been considered undruggable.
• OMO-103 is a novel miniprotein inhibitor targeting MYC.

Purpose of the Study:

• To assess the safety and tolerability of OMO-103 in patients with advanced solid tumors.
• To determine the recommended Phase 2 dose (RP2D) and evaluate preliminary signs of antitumor activity and pharmacokinetics.

Main Methods:

• A Phase 1, open-label, dose-escalation study using a 3+3 design with weekly intravenous OMO-103 administration.
• 22 patients with advanced solid tumors were enrolled, treated until progression, with safety, pharmacokinetics, and activity assessed.
• Transcriptomic analysis and soluble factor identification were used for target engagement and response marker evaluation.

Main Results:

• OMO-103 was generally well-tolerated, with most common adverse events being grade 1 infusion-related reactions.
• One dose-limiting toxicity was observed at dose level 5 (DL5).
• Pharmacokinetics showed nonlinearity with signs of tissue saturation at DL5; 8 of 19 evaluable patients had stable disease, with one showing a 49% tumor volume reduction.

Conclusions:

• OMO-103 is a safe and tolerable MYC inhibitor with early signs of clinical activity in advanced solid tumors.
• The recommended Phase 2 dose was determined to be DL5 (6.48 mg/kg).
• Further investigation in Phase 2 trials is warranted to confirm efficacy and identify predictive biomarkers.