Amivantamab shows robust efficacy in post-platinum therapy patients with EGFR Ex20ins NSCLC

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Published: 11 Apr 2023
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Prof Nicolas Girard - Institut Curie, Paris, France

Prof Nicolas Girard speaks to ecancer about the long-term efficacy, safety, and predictors of response to amivantamab among patients with post-platinum EGFR Ex20ins-mutated advanced non-small cell lung cancer (NSCLC).

He outlines the background and methodology of this study. Prof Girad explains that there is currently a lack of standard of care treatments for EGFR Ex20ins-mutated advanced NSCLC. As of Sep 2022, investigator-assessed overall response rate was 37% and no new safety signals were detected.

Prof Girad concludes that amivantamab demonstrated robust efficacy that was consistently observed across post-platinum patients with EGFR Ex20ins NSCLC, including the elderly, those with multiple prior lines, or those who were platinum sensitive or refractory.


CHRYSALIS is a phase I/II study assessing amivantamab, which is a bi-specific antibody targeting EGFR and MET, so a dual blocking of the EGFR protein and blocking also the interaction of EGFR with MET which are key in the signal transduction from the extracellular domain to the intracellular domain of the EGFR receptor. This antibody, amivantamab, was assessed in this study in a subgroup of patients with EGFR mutant non-small cell lung cancer which is the group of patients with EGFR exon 20 insertion mutations. So, this is the most frequent uncommon EGFR mutation. We have the common EGFR mutations L858R and exon 19 for which TKIs are standard of care but we have these uncommon, less frequent mutations, mostly consisting of EGFR exon 20 insertion mutations, for which we do not have any standard of care historically. The EGFR TKIs are not working for these patients.

So, this is a cohort of 114 patients from the CHRYSALIS phase I/II study. Patients with advanced refractory non-small cell lung cancer showing disease progression after at least one line of platinum-based chemotherapy. In this setting we do not have any kind of standard of care; we have some kinds of real-world options including single agent chemotherapy. But here we are assessing amivantamab which is designed to target this complex EGFR mutation.

These are the updated data because amivantamab data were presented two years ago and published already. Very interesting to see that the overall response rate with amivantamab in those patients with advanced non-small cell lung cancer with EGFR exon 20 insertion mutations is as high as 37% and the median duration of response is just above one year, it’s 12.5 months. The response rate was pretty similar across key subgroups and we also have the updated PFS and OS. Very interesting to see that two-year overall survival is 14%; the two-year overall survival is 47% so it means that one third of alive patients at two years are still in control of their disease with amivantamab.

Very interesting data because amivantamab is not approved in Europe, in the US, in this setting, failure of platinum-based chemotherapy for patients with advanced metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. So this reinforces the data and the long-term benefit that we can have with this drug. There are other agents currently being developed in the EGFR exon 20 insertion mutations – mobocertinib, which is approved in the US, and other new compounds to clinical trials.

This was second line and we know that we will have as soon as possible data in the first-line setting with two different strategies. Amivantamab is currently being assessed in the first line in combination with chemotherapy, platinum plus pemetrexed plus amivantamab versus platinum pemetrexed, or to replace chemotherapy and this is with mobocertinib in the first-line setting versus chemotherapy. So this is very interesting because these data reinforce the benefit here with amivantamab. We know that we may also have this long-term benefit in patients in the refractory setting switching to the first-line setting. At the end it also reinforces this data, reinforces the current use of the drug in the second-line setting.