Anti-tumour activity of TAK-788 in NSCLC patients with EGFR exon 20 insertions

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Published: 18 Jun 2019
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Dr Joel Neal - Stanford University, Stanford, USA

Dr Joel Neal talks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about a study looking at the anti-tumour activity of oral investigational EGFR/HER2 inhibitor TAK-788 in NSCLC patients with EGFR exon 20 insertions.

He explains that EGFR mutant NSCLC with exon 20 insertions is a very particular type of the cancer.

It makes up only 5% of EGFR mutant lung cancer with EGFR mutant lung cancer making up just 15% of NSCLC.

Dr Neal explains that the data presented is mainly from one of the extension cohorts and that out of these patients a 43% response rate was seen, comparing favourably to other drugs in its class.

It’s exciting to talk about this work just presented by Greg Riely about a new drug, TAK-788, in non-small cell lung cancer. It’s for a very, very particular type of non-small cell lung cancer, EGFR mutant lung cancer with exon 20 insertion mutation, so only 5% of EGFR mutant lung cancer overall and EGFR mutant lung cancer is only about a 15% slice of the non-small cell lung cancer pie overall.

This was a phase I and phase II clinical trial so phase I trying to find the right dose of the drug and there were a number of different expansion cohorts, over ten different expansion cohorts, ultimately settling on 160mg every day as the maximally tolerated dose. Then that dose was selected and moved into a number of extension cohorts and these data are mainly presenting the data from one of those extension cohorts, a total of 28 patients who received the drug.

Out of those 28 patients the responses seen, radiographic responses of tumour, were seen in 43% of patients and the progression free survival time was 7.3 months. This compares favourably to other drugs in its class and much, much better than we expected from other EGFR inhibitors out there.

Was there an association between TAK-788 and the response of it and particular EGFR insertions?

Within the EGFR exon 20 insertion mutations we did look at the subtype although clinically we tend to categorise all of these together. It didn’t look like there was any clear association of any of the subtype mutations having a response.

How does the efficacy of this drug compare with other EGFR tyrosine kinase inhibitors?

What’s unique about EGFR exon 20 insertion non-small cell lung cancer is that the FDA approved EGFR tyrosine kinase inhibitors have been tested but are minimally to not effective in this type of non-small cell lung cancer. What’s also interesting is there are other drugs tested in this class and one of them, poziotinib, has some data presented. However, these data look a little bit stronger overall in terms of the numbers that we’ve seen overall.

Plasma biomarkers were not tested in this study although certainly plasma biomarkers have been developed as a way to detect this type of non-small cell lung cancer overall and could theoretically be used to follow responses over time.

So, overall, these are promising data. This is showing responses with a novel drug that’s potent and selective for a novel target. Right now there’s no FDA approved drug that seems to substitute for the effect that we’ve seen here so what’s going to happen is this drug is being moved into an extension cohort with many more patients being enrolled and the results of that will hopefully help validate this.

Overall this drug looked like it had toxicity very similar to what we see from other EGFR inhibitors – diarrhoea, some nausea, vomiting, some rash, as well as an unusual toxicity which was pancreatitis but mostly chemical pancreatitis not clinically significant. So it looks like a tolerable drug overall.