Mariposa-2: Amivantamab Following Progression on Osimertinib in EGFR-Mutated NSCLC

Mariposa 2 trial addressed advanced non-small cell lung cancer post-Ozimertinib. Amivantamab with/without Lazertinib showed improved survival, signaling a potential new standard of care.

Author: Dr Antonio Passaro (on-camera comments) - Courtesy of

At the ESMO 2023 conference, the results of the Phase three global randomized Mariposa 2 trial were presented. The trial focused on patients with advanced non-small cell lung cancer after progressing on Ozimertinib due to an EGFR mutation. The study aimed to evaluate Amivantamab combined with chemotherapy, with or without Lazertinib, compared to standard chemotherapy.

The trial involved 657 patients from various regions and aimed to assess progression-free survival. The primary endpoint was to compare the survival benefits among the different treatment arms. The study found a statistically significant improvement in progression-free survival with the combination of Amivantamab plus chemotherapy, both with and without Lazertinib, compared to standard chemotherapy. There was a notable reduction in the risk of disease progression or death, with response rates over 60% in the combination treatment arms, contrasting with the 36% response rate in the chemotherapy-alone arm.

The data also revealed a significant improvement in intracranial progression-free survival with the use of Amivantamab combined with chemotherapy, irrespective of the addition of A2 resin kinase inhibitors. The combination treatment demonstrated efficacy in controlling disease progression in the brain, particularly in patients who did not receive definitive radiotherapy.

Safety assessments indicated expected toxicities related to EGFR and met pathway due to the treatment. However, these side effects were manageable and did not limit the dosing. Venous thromboembolism incidence was low and consistent across the treatment arms.

Conclusively, the data presented suggests that the combination of Amivantamab with chemotherapy should be considered the new standard of care for patients with advanced non-small cell lung cancer who have progressed on or after Ozimertinib. The recommendation emphasizes considering the treatment's efficacy, safety, and notably, its impact on intracranial disease progression-free survival.