MYC targeting with a new agent in solid tumors

A 91-amino acid miniprotein, OMO-103, is a promising novel MYC inhibitor with potential benefit in patients with advanced solid tumors, as shown by a phase I trial recently published on Nature Medicine.

The MYC oncogene is seen as as an excellent therapeutic target but several technical difficulties, especially the intrinsically disordered nature of the protein, have so far prevented the development of a clinically viable MYC inhibitor. This study a first-in-human phase 1 clinical trial to assess the safety, pharmacokinetics and preliminary signs of activity of OMO-103, a first-in-modality anti-MYC miniprotein. Authors involved a total of 22 patients with a wide range of metastatic solid tumors who had received a median of four previous lines of treatment; the design of the study was a dose escalation of weekly intravenous, single-agent OMO-103 administration in 21-day cycles, encompassing six dose levels. The most common adverse events were grade 1 infusion-related reactions, occurring in ten patients and one dose-limiting toxicity occurred at dose level 5. 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. Based on all the data, the recommended phase 2 dose was determined as 6.48 mg/kg and authors say that «these findings and the safety profile of OMO-103 encourage further investigation of its clinical activity and safety in specific indications. In addition, a combination of MYC inhibition with other treatments, such as chemotherapy, personalized medicine and immunotherapy, could increase their efficacy both in contexts where MYC is not overexpressed as well as where it is amplified or overexpressed, a common mechanism of drug resistance». Researchers identified soluble factors that are potential pharmacodynamic and predictive response markers but «their validity and potential antitumorigenic role require further testing in a larger and more homogenous patient population. The identified signatures are indeed currently being tested in a new clinical study with OMO-103 in combination with standard-of-care chemotherapy , where the predictive signature is being used for patient selection», authors conclude.