The development of amivantamab for the treatment of non-small cell lung cancer
Danielle Brazel1, Misako Nagasaka2,3,4
1Scripps Clinic/Scripps Green Hospital, La Jolla, USA.
Abstract:
Non-small cell lung cancer (NSCLC) patients with sensitizing oncogenic driver mutations benefit from targeted therapies. Tyrosine kinase inhibitors are highly effective against classic sensitizing epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletions and exon 21 L858R point mutations. Conversely, EGFR exon 20 insertions (exon20ins) are resistant to the traditional EGFR tyrosine kinase inhibitors (TKIs). In May 2021, the US Federal Drug Administration (FDA) provided accelerated approval to amivantamab (Rybrevant) in adults with locally advanced or metastatic NSCLC with EGFR exon20ins after treatment with platinum-based chemotherapy. Amivantamab was the first EGFR/MET bispecific antibody to be approved specifically for EGFR exon20ins where there was an unmet need. Furthermore, amivantamab is being evaluated in additional settings such as post osimertinib in sensitizing EGFR mutations as well as in MET altered NSCLC. Here we discuss amivantamab in regard to its mechanism of action, preclinical and clinical data, and clinical impact for patients with EGFR exon20ins NSCLC and beyond.
Insights
Amivantamab is a new targeted therapy for non-small cell lung cancer (NSCLC) with specific EGFR exon 20 insertions. This bispecific antibody offers a new treatment option for patients resistant to traditional tyrosine kinase inhibitors.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) often harbors driver mutations.
- Classic epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs).
- EGFR exon 20 insertions (exon20ins) confer resistance to conventional EGFR TKIs, representing an unmet need.
Purpose of the Study:
- To review amivantamab's mechanism of action, clinical data, and impact.
- To highlight amivantamab as a novel therapy for EGFR exon20ins NSCLC.
- To discuss amivantamab's potential in other NSCLC settings.
Main Methods:
- Review of preclinical and clinical studies on amivantamab.
- Analysis of amivantamab's efficacy and safety data.
- Discussion of amivantamab's role in NSCLC treatment paradigms.
Main Results:
- Amivantamab is the first approved EGFR/MET bispecific antibody for EGFR exon20ins NSCLC.
- It received accelerated FDA approval for advanced or metastatic NSCLC post-chemotherapy.
- Amivantamab is being investigated in other EGFR mutation settings and MET-altered NSCLC.
Conclusions:
- Amivantamab addresses a critical unmet need in EGFR exon20ins NSCLC.
- It represents a significant advancement in targeted therapy for NSCLC.
- Further research will define amivantamab's broader clinical utility.
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