Treatment of MET Exon 14 Mutations in NSCLC


Heather Wakelee, MD, reviews key data for the treatment of MET exon 14 mutations in NSCLC as seen in the GeoMETry-III trial and the CRYSALIS study.

John V. Heymach, MD, PhD: We had some other disease spaces and updates and new data on that. We’ll go through these briefly. One is MET exon 14. We know that we have 2 drugs that are FDA approved for MET exon 14 non–small cell lung cancer. We have tepotinib and capmatinib. We’ve seen additional data for both drugs that support it. Heather, do you want to talk about the GeoMETry-III study? This is 1 comparing capmatinib with docetaxel, so what we’ve got coming through that.

Heather Wakelee, MD: I will, but I don’t have as much data on that 1. When we talk about comparisons and trying to figure out where a new treatment fits in to the landscape, somehow, we’re still in the world where absolutely everything has to get compared with docetaxel if we want to move it into second line. That does get a little frustrating because we’re trying to sort through. The real question with most agents is when is it first line and when is it later? The real questions are around TKIs [tyrosine kinase inhibitors] first. We know they work. We have beautiful response rates with these agents, so trying to do a head-to-head with docetaxel is less relevant, yet that’s what we’re often required to do by the FDA.

When I think about the patients we’ve had with MET exon 14 and trying to figure out first line, second line, and third line, how do we sequence these TKIs and where do we sequence with chemotherapy. This didn’t necessarily help with my thinking about that. It needs to be done, I guess, but why, right? That’s the question I have. Why are we stuck doing the same studies 20-plus years later?

John V. Heymach, MD, PhD: Right. You’re bringing up if a drug has a 40% or 50% response rate, and docetaxel has a 10% to 13% response rate. Do we really need to compare them every time?

Heather Wakelee, MD: No, I don’t think we need to keep doing that, but I’m not working for the FDA, so I’ll step back from that now and not ramble on. Clearly, capmatinib is active and tepotinib is active. We’ve seen benefit. I’d certainly be thinking about it before I give them docetaxel.

John V. Heymach, MD, PhD: Alright. Heather, we saw some activity for another type of drug, amivantamab, which you mentioned for MET exon 14. Do you want to talk about that?

Heather Wakelee, MD: We saw some encouraging data in small numbers. The total number of patients they report on was in the teens, but the response rate was over 60% in the patients who had tumors with MET exon 14 skipping mutations. These patients had all been previously treated, and they received the amivantamab. This is a MET antibody in addition to being an EGFR antibody, so it’s bispecific.

When you’re dealing with such small numbers, we make a big deal about response rates but keep in mind that when you’ve only got 14 patients and 9 respond, it takes only 1 other patient to respond or not respond and your response rates do this. Thus, we need to be careful. We’ve seen a lot of drugs that looked phenomenal in the first 10 patients and then fell off. It’s encouraging. It makes sense. We want to see that duration of response. Then it’s going to weigh the toxicity vs the toxicity of TKIs and try to figure out the sequencing. But it’s a very strong, encouraging early signal.

John V. Heymach, MD, PhD: Yes, that’s right.

Transcript Edited for Clarity

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