Amivantamab with lazertinib for patients with chemotherapy-naïve NSCLC with EGFR mutations who have experienced relapse on or after osimertinib therapy

By November 10, 2021No Comments

*August 2021*

DR LOVE: So let’s talk about some of the papers presented at ASCO related to targeted therapy, and one you commented on in your talk was the CHRYSALIS study looking at the amivantamab bispecific along with lazertinib, which I guess is a lot like osimertinib. Can you talk a little bit about this paper, and also a little bit more about amivantamab, and then generally speaking right now how you’re kind of thinking through that agent and using it in your practice?

DR NEAL: Yeah. We’ve got a version of this trial, actually, the CHRYSALIS-2 study, open at our institution, and we’ve just been calling it the ami/lazer trial.

DR LOVE: Yeah, that’s good.

DR NEAL: These agents get increasingly difficult to pronounce. Amivantamab is a MAB, it’s an antibody to EGFR-MET bispecific, so it’s actually got EGFR, like cetuximab or necitumumab for example, and an anti-MET. I don’t think there are any FDA-approved anti-MET antibodies at this point that aren’t antibody-drug conjugates. But this is just an antibody bispecific. Lazertinib is a T790M active EGFR-TKI, similar to osimertinib for most intents and purposes.

So amivantamab of course got FDA approved by itself in the single-agent use of EGFR exon 20 non-small cell lung cancer, so those EGFR exon 20 insertions which are not very targetable with other EGFR-TKIs that are currently FDA approved. It was FDA approved a couple of months ago in that single-agent setting. But this is in a different setting, EGFR-mutant non-small cell lung cancer, with classical EGFR mutations, exon 19 deletions or L858R, in patients that are resistant to EGFR-TKIs, getting the combination therapy.

And what Josh Bauml presented was that patients had response rates between 30% and even 90% looking at the subgroups of biomarker-selected patients. So oftentimes for EGFR resistance we’ll do a circulating tumor DNA assay to look for resistance, or I tend to favor tumor repeat biopsies to look for the DNA changes in the tumor itself, as well as histologic transformation changes.

But they did a whole new kind of assay that we’re not routinely doing looking for acquired resistance. It’s EGFR and MET immunohistochemistry separately. Remember, this is an EGFR-MET bispecific antibody, so looking for the targets in the tumor. Out of those patients that were EGFR-EMT dual positive by IHC, 9 out of 10 of them responded, 90% response rate. So it looked like interesting new predictive biomarker of response and supporting the fact that maybe tissue can yield more information. We can’t get IHC off of blood-based assays.

DR LOVE: But it looks like, if you look at the waterfall plot, and also response rate 29% when you don’t have EGFR or MET, and these patients are already on osimertinib, so the lazertinib shouldn’t be adding that much to that. So what happens when you just give amivantamab and keep the osimertinib going? I guess it might be the same thing?

DR NEAL: Yeah. Well, we don’t know. I don’t think the studies have been done combining amivantamab plus osimertinib. And ami by itself does have significant single-agent response rates in this patient population. So I believe ami is under FDA review by itself for the EGFR-mutant acquired resistance population here. And if it were approved by itself it’s not clear what the lazertinib is adding independently, the dual inhibition versus ami by itself.

Read the entire transcript or listen to the podcast here.