Phase I study of the safety, tolerability, and potential therapeutic dose of OMT-110 for patients with refractory metastatic Colorectal Cancer.

Abstract

Background: OMT-110 is a repositioned drug candidate for the treatment of metastatic colorectal cancer (mCRC). This phase I study aimed to determine the appropriate dose of OMT-110 for phase II trials and its safety, tolerability, and efficacy. We conducted the first-in-human dose-escalation study of patients with advanced mCRC (age 20 years or older) who had refractory disease.

Methods: OMT-110 was administered subcutaneously in a repeated cycle of 21 days on/seven days off until tumor progression, toxicity, or withdrawal. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria ver4.03. The pharmacokinetic profiles were determined before and after OMT-110 administration. Pharmacodynamic and efficacy evaluations were performed using abdominopelvic computed tomography (APCT), chest CT, and ¹⁸F-FDG-Positron emission tomography/CT, following the Response Evaluation Criteria in Solid Tumors v1.1. Fourteen patients were divided into four cohorts to receive doses ranging from 12.5 mg to 100 mg daily.

Results: Based on our results, a daily dose of 100 mg is recommended following a repeated 28-day treatment cycle of 21 days on/seven days off. Of the 54 adverse events experienced by the participants in the safety set, all were grade 1 or 2, except for two serious adverse events. OMT-110 was either "unrelated" or "definitely not related" or "probably unrelated" to these events. Pharmacokinetic analysis revealed no apparent accumulation.

Conclusions: Based on the evaluation of pharmacodynamic and efficacy parameters, OMT-110 is a promising novel systemic therapy with potential immunomodulatory effects for patients with advanced mCRC.

Trial registration: CRIS Registration Number KCT0005336 (first posted on 08/08/2017).