Sym015 shows superior specificity compared to TKIs for NSCLC

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Published: 29 May 2020
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Dr Ross Camidge - University of Colorado Cancer Center, Aurora, USA

Dr Ross Camdige speaks to ecancer online about his ASCO 2020 virtual presentation which discussed Sym015 for NSCLC.

Sym015, a mixture of 2 humanised antibodies, triggers MET degradation by a unique mechanism with superior specificity compared to tyrosine kinase inhibitors (TKIs).

Combination with MET TKI to delay or prevent resistance should be further explored.

There are MET addicted subtypes of non-small cell lung cancer; high level MET amplification but perhaps more prominently MET exon 14 skip mutations which is about 4% of lung cancer. There is a range of tyrosine kinase inhibitors, most of them are what is called class 1 inhibitors – crizotinib, tepotinib and the most recently FDA approved one which is capmatinib. There are also some class 2 inhibitors but none of those are actually licensed – cabozantinib is sitting in the pharmacy although it’s a relatively poorly tolerated drug.

These drugs are good but you all develop acquired resistance and some of those resistance mechanisms are on target – you get MET mutations. You can sometimes change between class 1 to class 2 but another approach is whether you attack MET with an antibody.

Symphogen 015 is a mixture of two different MET antibodies and although, yes, it shows great activity in those who are untreated with a MET inhibitor, as you might expect, who is going to go for an intravenous drug as opposed to a pill. But what’s exciting about this presentation is a relatively small number of cases of patients who had been previously exposed to a MET tyrosine kinase inhibitor, had developed acquired resistance, including at least one who had definable MET mutations. You could show that their cancer shrunk, it didn’t quite achieve an objective response, but you could show that those mutations went down in circulating free DNA. So these antibodies may have a role either in the acquired resistance setting or possibly in combination with the tyrosine kinase inhibitors up front.