Publication date: 25/09/2019
OCTIMET Oncology NV, the Belgian life science company with a focus on accelerated development of highly selective differentiated MET kinase inhibitors is pleased to announce the recruitment of the first patient into the second module of its phase I/II clinical study in patients with advanced solid malignancies.
The Study (NCT03138083) is currently evaluating OMO-1 in a monotherapy setting as well as in combination with small molecule EGFR tyrosine kinase inhibitors (TKIs). OMO-1 is an oral, highly selective small molecule MET kinase inhibitor that has demonstrated potent single agent and combination activity in a range of preclinical models. OCTIMET obtained a worldwide exclusive license to OMO-1 from Janssen Pharmaceuticals which had previously carried out a healthy volunteer trial where predicted efficacious exposures were reached without any significant adverse events.
The primary objective of Module 2 of this Phase I/II study is to demonstrate that OMO-1, in combination with EGFR TKIs, has an acceptable safety and tolerability profile in patients with advanced MET amplified cancer types, whose tumours are progressing during treatment with an EGFR-TKI; secondary objectives include determination of pharmacokinetic (PK) characteristics, and indication of clinical efficacy at doses and schedules at or below the monotherapy recommended phase 2 dose (RP2D). Preliminary top-line results of the combination of OMO-1 with EGFR TKIs are expected in 2020.
This adaptive study, with an innovative modular design, is being conducted in different countries across Europe and the USA.
Glen Clack, CMO of OCTIMET: “MET amplification is known to be a key driver of resistance to EGFR TKIs. This study module will explore the combination of OMO-1, a differentiated selective MET kinase inhibitor, with EGFR TKIs, and provide clear clinical proof of concept data for this combination.”
Shelley Margetson, CEO, of OCTIMET added: “This adaptive clinical trial with patient cohorts enriched for validated and highly relevant biomarkers is the hallmark of OCTIMET’s accelerated development approach and illustrates how we are striving to get effective drugs to the right patients as fast as possible.”
About the Study, NCT03138083
The study is a modular, multi-arm, multi-part, open label, first in human study to evaluate the safety and tolerability of OMO-1, alone and in combination with anti-cancer treatments, in patients with locally advanced, unresectable or metastatic solid malignancies.
The study will consist of a number of study modules - the first of which is Module 1, a monotherapy module to be followed by further modules studying OMO-1 in combinations with other oncology drugs to address developing resistance to or progression on current treatment as well as possible synergistic effects.
In Module 1 of the first-in-patient study, OMO-1 monotherapy has shown a favourable safety profile at a recommended phase 2 dose (RP2D) of 250mg BD and a first expansion cohort for MET exon 14 mutated NSCLC patients is currently enrolling at that dose (DOI: 0.1200/JCO.2019.37.15_suppl.3062, Lolkema et al. Journal of Clinical Oncology 37, no. 15_suppl [May 20 2019] 3062-3062).
About EGFR Tyrosine Kinase Inhibitors
Lung cancer is the leading cause of cancer-related mortality worldwide. Of all lung cancer cases, 80–85% are non-small-cell lung cancers (NSCLC), and the majority of these cases are in advanced or metastatic stage (III or IV) at the time of diagnosis. Among these patients with NSCLC, a substantial number are harboring activating EGFR mutations, ranging from 10% in Europe to 38.4% in Asia. During the past years, EGFR tyrosine kinase inhibitors (TKIs) have been developed and have become standard first-line treatment for patients with EGFR mutation-positive NSCLC. Various trials showed higher response rates and improved progression-free survival (PFS) for first-line treatment with the EGFR TKIs afatinib, erlotinib, and gefitinib compared to platinum-based doublet therapy in patients with activating EGFR-mutated (exon 19 deletion or exon 21 L858R mutation) NSCLC. Recently, in head-tohead trials, the newer EGFR TKIs, dacomitinib and osimertinib, showed a significantly longer PFS compared to standard EGFR-TKIs, while dacomitinib, a second-generation EGFR-TKI, had a better efficacy compared to gefitinib, and osimertinib showed a more favorable PFS compared to standard EGFR-TKI (gefitinib or erlotinib). MET amplification is known to be a common driver of resistance to EGFR TKIs.
OCTIMET Oncology NV acts as a translational accelerator, focusing on creating value for patients and investors by providing rapid clinical proof of concept for cancer therapies through innovative clinical development strategies and patient centred biomarker approaches. OCTIMET was set-up in 2016 and is backed by leading national and international life sciences investors. OCTIMET licensed three patent families related to highly selective MET kinase inhibitors from Janssen Pharmaceutical companies of Johnson and Johnson in January 2017. OCTIMET is based at the JLABS @ BE facility in Beerse (Belgium). The current focus is on its clinical stage lead asset OMO-1, a highly selective small molecule MET kinase inhibitor that is developed using specific patient selection biomarkers. For more information: www.octimet.com