Catherine A. Shu, MD, on Amivantamab Plus Lazertinib in Previously Treated EGFR+ NSCLC

At ASCO 2022, Catherine A. Shu, MD, spoke about the CHRYSALIS-2 trial which investigated the use of amivantamab plus lazertinib in patients with EGFR-mutant non–small cell lung cancer following progression on a prior EGFR inhibitor.

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Catherine A. Shu, MD, presented updated findings from cohort A of the phase 1 CHRYSALIS-2 trial (NCT04077463) in patients with non–small cell lung cancer harboring and EGFR exon 19 deletion or L858R mutation who received amivantamab (Rybrevant) plus lazertinib (Laclaza) after treatment with osimertinib (Tagrisso) and platinum-based chemotherapy in prior settings.1

At the median follow-up of 10.0 months (95% CI, 4.2-6.9), the median progression-free survival was 5.1 months (95% CI, 4.2-6.9) with a median overall survival of 14.8 months (95% CI, 12.1-NE). Adverse effects (AEs) were mostly grade 1 and 2, with pneumonitis or interstitial lung disease being present in 7% of patients at all grades and in 4% at grade 3 or higher. Rash occurred in 80% of patients, 10% being grade 3 or higher. Overall, the safety profile was consistent with what was previously reported.

Catherine A. Shu, MD, clinical director of the Thoracic Medical Oncology Service at Columbia University Herbert Irving Comprehensive Cancer Center, spoke to CancerNetwork® in an interview regarding these updated findings. “The most important thing to take away was that the response rate was good [at around] 33%. This is for a population of patients who have exhausted their standard of care options, and we’re seeing not only good response rates but also a very durable response,” Shu said.

CancerNetwork®: What was the rationale for using amivantamab and osimertinib in EGFR-positive non–small cell lung cancer?

Shu: Amivantamab is a novel drug. It’s a bispecific antibody that targets both EGFR and MET. It’s now been approved for NSCLC with EGFR exon 20 insertion mutations.2 Based on its mechanism of action, we are exploring its usage in other areas, including [NSCLC harboring] EGFR exon 19 and L858R. We’re also exploring it in MET exon 14–mutant cancers, so a variety of different areas. For patients with your classical EGFR mutations like exon 19 deletion or L858R, we have an unmet need after osimertinib and platinum-based chemotherapy.

What were the updated findings of the CHRYSALIS-2 trial?

This is an important cohort of patients to look at. Patients with EGFR [mutations] typically start with osimertinib and then go on to platinum-based chemotherapy. After that we don’t have a great next line of treatment. In cohort A of CHRYSALIS-2, we’re looking at the combination of amivantamab plus lazertinib. It’s interesting because we’re using a bispecific antibody and we’re adding it to a third-generation TKI [tyrosine kinase inhibitor].

What was the toxicity profile like?

Rash occurred in up to 80% of patients, although the rate of grade 3 and 4 rash was much lower. Another interesting adverse event was infusion-related reactions, and that’s something that we’ve seen with amivantamab monotherapy. It tends to happen just on that first treatment. Now that we [have experience administering it], we know how to mitigate those infusion-related reactions and most patients don’t get it again after the first day. I would say even though that’s a common adverse event, it is something we know how to mitigate. All in all, the safety profiles didn’t show anything new, although the rash was probably the most significant thing.

What other findings stood out to you?

An important point to make is that we saw stable disease in 43% of our patients, so the clinical benefit rate was high. For patients with an unmet need, this is an exciting new therapy that we can offer them.

Are there any plans for future trials?

There are a few other trials that are ongoing, like MARIPOSA [NCT04487080] and MARIPOSA-2 [NCT04988295] which are looking at amivantamab and lazertinib and amivantamab, lazertinib, and chemotherapy combination, respectively, in the front-line [setting].

What should your colleagues take away from this presentation?

My take home is that this regimen of amivantamab plus lazertinib is active. We’re clearly seeing responses in patients who have progressed on chemotherapy and osimertinib in the past. Not only are we seeing responses, but the responses are durable and the drugs are safe and tolerable overall. It gives us another option for our patients which is what all of us are trying to do.

Is there anything else you would like to highlight from this presentation?

The other interesting thing is that this was in a heavily pretreated patient population. We had 2 sets of patients. One was just pretreated with osimertinib and chemotherapy only and then the other was a more heavily pretreated patient population. Some of those patients had up to 14 lines of prior therapy, showing that we can still get a good response rate in patients who have been heavily pretreated. This is a chemotherapy-free regimen which a lot of our patients are looking for. The last thing is that we did all this without biomarker selection. We didn’t need a particular biomarker to see a response. For future studies, we’re still examining what biomarkers may be the best but for now, we’re seeing responses in patients with EGFR- and MET-based mechanisms of resistance and other unknown mechanisms of resistance, but there’s no clear biomarker yet.


  1. Shu CA, Goto K, Ohe Y, et al. Amivantamab and lazertinib in patients with EGFR-mutant non–small cell lung (NSCLC) after progression on osimertinib and platinum-based chemotherapy: Updated results from CHRYSALIS-2. J Clin Oncol. 2022;40(suppl 16):9006. doi:10.1200/JCO.2022.40.16_suppl.9006
  2. FDA grants accelerated approval to amivantamab-vmjw for metastatic non-small cell lung cancer. News Release. FDA. May 21, 2021. Accessed September 14, 2022.