Landmark PALOMA and MARIPOSA Studies Reveal the Impact of Amivantamab Alone and Combined with Lazertinib in Advanced NSCLC

Abstract

Mutations in the epidermal growth factor receptor (*EGFR*) gene are frequently detected in non-small cell lung cancer (NSCLC). The most common *EGFR* mutations include deletions in exon 19 (Ex19del) and point L858R mutations in exon 21. Among uncommon mutations, exon 20 insertions (Ex20ins) account for approximately 10% of *EGFR*-mutant NSCLC cases. Bispecific antibodies have demonstrated potential in the treatment of NSCLC by adopting a dual-targeting approach to enhance therapeutic efficacy. Several important updates on the use of bispecific antibodies in NSCLC management were presented at the 2024 European Lung Cancer Congress (ELCC 2024) held in Prague, Czech Republic, on March 20−23, 2024. Amivantamab is a bispecific antibody that targets both EGFR and mesenchymal epithelial transition (MET) receptor with the capability to activate immune cells. It is approved for use as a single-agent therapy by Swissmedic and the European Medicinal Agency (EMA) for the treatment of adult patients with locally advanced or metastatic NSCLC with activating *EGFR* Ex20ins mutations after the failure of platinum-based chemotherapy. This mini-review summarizes the recent results of the phase II PALOMA study, which investigated a novel dosing strategy for amivantamab in advanced solid tumors, including NSCLC, and the phase III MARIPOSA trial, which evaluated the combination of amivantamab with lazertinib versus osimertinib in treatment-naïve advanced or metastatic NSCLC harboring common *EGFR* mutations (Ex19del and L858R). PEER REVIEWED ARTICLE **Peer reviewers:** PD Dr Michael Mark, Cantonal Hospital Graubünden, Chur, Switzerland One anonymous peer reviewer Received on May 13, 2024; accepted after peer review on June 14, 2024; published online on June 28, 2024.