Evaluating Amivantamab/Lazertinib Combo in EGFR-Mutant NSCLC

Alexander Spira, MD, PhD, FACP, director of the Virginia Cancer Specialists Research Institute, discusses the rationale for combining amivantamab-vmjw (Rybrevant) and lazertinib (Leclaza) for the treatment of relapsed or refractory EGFR-mutant non–small cell lung cancer (NSCLC).

There are currently very few treatment options for patients with relapsed/refractory NSCLC harboring EGFR mutations. Because of this, investigators are asssesing the combination of amivantamab, lazertinib, carboplatin, and pemetrexed (Alimta) in patients who have progressed after treatment with osimertinib (Tagrisso) and chemotherapy.

According to findings of the phase 1 CHRYSALIS-2 trial (NCT04077463) which evaluated the combination, encouraging responses were observed in patients who were pretreated with EGFR-mutant NSCLC. These data were presented at the 2022 IASLC World Conference on Lung Cancer.

Transcription:

0:08 | The goal of this is a couple fold. Number 1 is amivantamab is an antibody, so it works in a different mechanism of action than osimertinib. In theory, it should be able to overcome resistance. It binds EGFR at the cell surface, so it can overcome any intracellular mechanisms of resistance.

0:27 | The addition of osertinib has a couple of rationales. Number 1, it is is pretty well tolerated. Number 2 is not all cancer cells become resistant at the same time, so you're attacking it in a couple of different ways. The other real advantages that we hope and we know is that lazertinib has central nervous system penetration, so can help maintain central nervous system, ie brain responses, in this patient population, where amivantamab by itself does not do such a good job. One of the big things about osimertinib is that it has central nervous system penetration, so we'd like to keep that.