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A Phase I Trial of the Dual MET Kinase/OCT-2 Inhibitor OMO-1 in Metastatic Solid Malignancies Including MET Exon 14
Melinda A Pruis1, Matthew G Krebs2, Ruth Plummer3
1Department of Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Introduction:
Targeted therapy in non-small cell lung cancer (NSCLC) patients with mesenchymal epithelial transition (MET) exon 14 skipping mutations (METex14) and MET amplifications has improved patients' outcomes. The development of more potent MET kinase inhibitors could further benefit these patients. The aim of this trial is to determine the safety and recommended phase 2 dose (RP2D) of OMO-1 (an oral dual MET kinase/OCT-2 inhibitor) and to assess preliminary clinical efficacy in METex14-positive NSCLC and other MET-positive solid tumors.
Materials And Methods:
This was a first-in-patient, open-label, multicenter study of OMO-1 in patients with locally advanced or metastatic solid malignancies. A standard 3 + 3 dose escalation design was utilized starting at a dose level of 100 mg BID continuously. Preliminary efficacy was investigated in patients with METex14-positive NSCLC, and MET amplified NSCLC and other solid tumors (MET basket).
Results:
In the dose-escalation part, 24 patients were included in 5 dose levels ranging from 100 mg twice daily (BID) to 400 mg BID. Most common adverse events (≥ 20%) were nausea, fatigue, vomiting, increased blood creatinine, and headache. The RP2D was determined at 250 mg BID. In the expansion cohorts, 15 patients were included (10 in METex14-positive NSCLC cohort and 5 in MET basket cohort) and received either 200 or 250 mg BID. Eight out of the 10 patients with METex14 positive NSCLC had stable disease as the best response.
Conclusion:
OMO-1 was tolerated at the dose of 250 mg BID and shows initial signs of MET inhibition and anti-tumor activity in METex14 mutated NSCLC patients.
Insights
A new oral dual MET kinase/OCT-2 inhibitor, OMO-1, shows promise for non-small cell lung cancer (NSCLC) patients with MET alterations. The recommended dose is 250 mg twice daily, with early signs of anti-tumor activity observed.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Targeted therapies for non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations (METex14) and MET amplifications have improved patient outcomes.
- Development of novel, potent MET kinase inhibitors is crucial for further enhancing patient benefit.
- OMO-1 is an oral dual MET kinase/OCT-2 inhibitor designed for these patient populations.
Purpose of the Study:
- To determine the safety and recommended phase 2 dose (RP2D) of OMO-1.
- To assess the preliminary clinical efficacy of OMO-1 in patients with METex14-positive NSCLC and other MET-positive solid tumors.
Main Methods:
- A first-in-patient, open-label, multicenter study utilizing a 3+3 dose escalation design.
- Dose levels ranged from 100 mg twice daily (BID) to 400 mg BID.
- Preliminary efficacy was evaluated in METex14-positive NSCLC and a MET basket cohort.
Main Results:
- Twenty-four patients were enrolled in dose escalation across five dose levels.
- The most common adverse events (≥20%) included nausea, fatigue, vomiting, increased creatinine, and headache.
- The RP2D was established at 250 mg BID. In expansion cohorts, 8/10 METex14-positive NSCLC patients achieved stable disease.
Conclusions:
- OMO-1 demonstrated tolerability at the 250 mg BID dose.
- The study observed initial signs of MET inhibition and anti-tumor activity in METex14-mutated NSCLC patients.
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