This ASCO we presented abstracts on a new compound which is called OMO-1, it’s an inhibitor, a strong, selective inhibitor, of the cMET protein and especially targeting patients with cMET aberrations. These are actually in lung cancer patients at present, very low frequencies, but these mutations are weird mutations, they are exon 14 skipping mutations they call them. So it’s a little bit difficult to detect them but if you detect these patients they are actually cMET driven cancers so it’s very important that we get novel drugs that actually target that pathway.
OMO-1 does that and what we presented at this ASCO is that it’s tolerated, the drug, we can give it, it’s actually delivered and we provide proof of concept that actually the drug also gives responses in patients with those exon 14 mutations.
What endpoints or outcomes were assessed?
It’s a real phase I study so the first part really was about tolerability and finding the right dose of the drug. That was actually done in an all comer population so very few responses were seen. So then we went into an enrichment cohort for exon 14 patients and there actually we did see some responses. The primary outcomes were tolerability but also looking at efficacy in the sense of response to treatment. Importantly, also the biomarker outcomes where we took biopsies, serial biopsies of patients with the exon 14 mutations and we could show that the drug is actually there and it is actually hitting the target. So that’s really interesting information.
Were there any specific adverse events at all?
The drug by itself has a fairly well tolerated adverse event profile. When you really go up in those you see some weird events where patients have flu-like symptoms and cytokine release problems. But if you give it at the dose where the MTD is actually the side effects are really well manageable and mainly gastrointestinal side effects such as nausea and vomiting.
What was the optimal dose of this drug?
We ended up giving our patients 250mg b.i.d. whether that really is the optimal dose we’ll have to see but that’s currently the selected dose for future development.
What are the next steps for this research?
The next steps will be that we’re going to be able to expand the number of patients with those exon 14 mutations. That’s really crucial to show proof of concept that this drug inhibits the driver mutation in these patients. But then soon after that we’ll go into a very much expanded programme where we’re going to combine it with other compounds. The first one to combine it with is EGFR inhibitors because cMET amplification or cMET signalling is one of the mechanisms by which patients become resistant to EGFR inhibition.