Amivantamab for the Treatment of EGFR Exon 20 Insertions in NSCLC

EP: 1.Overview of Advanced NSCLC with EGFR Mutations Including Exon 20 Insertions

EP: 2.Testing for the EGFR Exon 20 Insertion

EP: 3.Historical Treatment Approach for EGFR Exon 20 Insertions in NSCLC

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EP: 4.Amivantamab for the Treatment of EGFR Exon 20 Insertions in NSCLC

EP: 5.Mobocertinib for the Treatment of EGFR Exon 20 Insertions in NSCLC

EP: 6.Treatment Selection for Patients With EGFR Exon 20 Insertions in NSCLC

EP: 7.Unmet Needs and Future Directions

EP: 8.Recap: Targeted Therapies for EGFR Exon 20 Insertion-Positive NSCLC

EP: 9.OncView™ Podcast: EGFR Exon 20 Insertion as a Therapeutic Target in NSCLC

Mathew Fowler: Let’s look at amivantamab. Could you describe the mechanism of action of this drug and also get into the patient population trial design and important data that led to its approval in May 2021?

Zofia Piotrowska, MD: We were very excited to see amivantamab receive accelerated approval by the FDA. It was the first therapy specifically approved for patients with EGFR exon 20 insertion–positive non–small cell lung cancer. It was approved for patients who have progressed on prior platinum-based chemotherapy. When we think about how to treat these options, it’s important to remember that this is a second-line or later option. Amivantamab is a bispecific antibody targeting EGFR and MET, and it was approved based on the results of the CHRYSALIS trial, which was recently published by Dr [Keunchil] Park and colleagues in JCO [Journal of Clinical Oncology] in 2021. In the CHRYSALIS trial, 81 patients with EGFR exon 20 insertion–mutant non–small cell lung cancer who had received prior platinum-based chemotherapy were treated with amivantamab. We saw in that population that the response rate to amivantamab was 40%. The median duration of response was 11 months, and the median progression-free survival was 8.3 months. These are encouraging data in this population where targeted therapy options have previously been limited. We did see with amivantamab that there were some toxicities, as you might expect with an antibody targeting EGFR and MET. The most common toxicities that we’re seeing included rash. About 86% of patients had rashes, although many of these were low-grade. When using amivantamab, about two-thirds of patients had infusion-related reactions. These seemed to be most common on cycle 1, day 1, with the initial treatment. There are guidelines in the package insert to mitigate these infusion reactions, including premedication, split-dosing over cycle 1, day 2 and day 2. It’s something important to be aware of and counsel patients about when treating with amivantamab.

Mathew Fowler: What’s the significance or the impact of this approval for patients with EGFR exon 20 insertions?

Zofia Piotrowska, MD: It’s great to have another option for patients with these mutations, and this is a very good option. It’s approved for second-line and later use, so it doesn’t necessarily impact our first-line treatment for patients with EGFR exon 20 insertions. But it’s a very good option to consider for patients who have received platinum-based chemotherapy and are looking for a second- or later-line option.

Transcript edited for clarity.