NSCLC Targeted Therapy: EGFR Exon 20 Mutation - Episode 4

Use of Amivantamab in patients with EGFR Exon 20–Positive Non–Small Cell Lung Cancer


An expert in the lung cancer and a representative from lung cancer advocacy group talk about the use of amivantamab, a novel therapy approved for treating EGFR exon 20 insertion–positive disease.


Estelamari Rodriguez, M.D., MPH: Amivantamab is one of these drugs that was recently approved. It’s interesting because when we think of targeted therapies, many of these therapies have been oral drugs, and this is a drug that is given by vein, intravenously. It works in an interesting way; it’s a bispecific, meaning that it binds two receptors. It binds an EGFR receptor, which is the one of interest, and another receptor called c-Met, that is a receptor that usually gets overexpressed when patients are failing EGFR therapy. It potentially has this dual effect on these receptors that drive lung cancer in EGFR-driven lung cancer. It obtained accelerated approval by the FDA. It was the first drug that got the approval because it showed dramatic responses in patients who have failed multiple lines of therapy. This approval was based on a phase 1 trial. Phase 1 trials are where patients who are running out of options, in a way, are looking for alternatives. We don’t know how the drugs are going to work, but we need patients to be enrolled to find out and get the right dose. This is one of these phase 1 trials where patients are getting a new drug to find out how it is tolerated.

This is called the CHRYSALIS multiple cohort trial and enrolled patients with amivantamab. They find out the recommended dose, which is later tested in an expanded phase 2 study. They had doses based on the weight of the patient, and what they showed was a remarkable response in patients who were failing everything else. They had a response rate of around 40%, so four out of 10 people were responding. Then the progression-free survival for patients who had failed many treatments was around eight months, but what’s more important is that with the patients who were responding, those responses were lasting close to a year. Those are averages and those are small studies, but they were significant enough findings that this drug was approved, with accelerated approval. What is important to note about this drug that is different is that instead of like other targeted therapies that you take at home by mouth, and you have to worry about GI [gastrointestinal] side effects, meaning any nausea or diarrhea, amivantamab is by vein, and it doesn’t cause hair loss and the traditional things we think of regarding chemotherapy. However, it can cause an infusion reaction, which is almost like an allergic reaction, that can be mitigated if you split the dose into two days.

I have treated patients in my practice, and we have seen it’s almost like hives in some patients. Some patients experience mild shortness of breath, but if you pretreat them with steroids, you can decrease that allergic reaction. The second time you take the drug, then you rarely see any reaction. I tell patients, the first time we’re going to be closely monitoring you and sitting by the bedside with you just in case, and you’re going to have all these premedications, but then after that, it will be much easier. The rate of infusion reactions with the next dose was less than 1%, so it’s very manageable.

If you’re someone who has difficulty getting to a cancer center, then the next drug that got approved, which is called mobocertinib, may be a drug that would be of interest, because that’s an oral drug that targets the EGFR 20 insertion receptor. That drug doesn’t have the infusion reactions, but more of the traditional side effects that we have seen, such as rash and diarrhea.

Transcript edited for clarity.