Ep. 2: New Insights From the MARIPOSA Trial: Amivantamab Plus Lazertinib for EGFR-Mutated NSCLC
Key Points
-
Expert discussion on the FDA approval of amivantamab plus lazertinib as frontline therapy for metastatic EGFR-mutated non-small cell lung cancer.
-
How amivantamab combines EGFR/MET blockade with immune-like mechanisms of action.
-
Exploring central nervous system monitoring performed in the MARIPOSA trial to understand agent activity in the brain.
At the 2025 American Society of Clinical Oncology Annual Meeting, Rahul Gosain, MD, MBA, and Rohit Gosain, MD, of the Oncology Brothers podcast, led a panel of experts in a detailed discussion on metastatic EGFR-mutated non-small cell lung cancer (NSCLC).
Joshua Sabari, MD, of Perlmutter Cancer Center NYU Langone Health, New York, New York, explored amivantamab, a bispecific antibody against EGFR and MET , and data from the pivotal MARIPOSA trial.
MARIPOSA enrolled patients with metastatic NSCLC with two common EGFR alterations, exon 19 deletion or L858R mutation. Participants were randomized between 1 of 3 treatment arms: amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.
The amivantamab plus lazertinib arm showed improved progression-free survival (PFS) and overall survival compared with the osimertinib control arm, and the FDA subsequently approved the combination regimen in the frontline setting.
Amivantamab’s efficacy is driven by ligand inhibition and receptor degradation mechanisms, and also a “very exciting sort of immune activity” via a process called trogocytosis, Dr. Sabari described.
Helena Yu, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, expanded on the inclusion of central nervous system (CNS) monitoring for all participants in the MARIPOSA trial protocol.
She explained that more than 50% of patients with EGFR-mutated NSCLC will develop brain metastases. However, CNS imaging is typically only done after brain metastases are identified.
While the additional imaging could have impacted some study end points like PFS, Dr. Yu noted the data may provide oncologists a greater understanding of asymptomatic CNS progression, how amivantamab penetrates the brain, and how patients may respond to therapy overall.