About the MARIPOSA Trial

The MARIPOSA trial is a phase 3 clinical study investigating the efficacy of a first-line treatment regimen combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR tyrosine kinase inhibitor, for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). The trial compares this combination to the current standard treatment, osimertinib, focusing on progression-free survival (PFS) and overall survival (OS) outcomes. The study has shown the combination therapy to be effective, offering a statistically significant improvement in median PFS, particularly in high-risk patients with brain metastases, liver metastases, and TP53 co-mutations. These findings suggest a potentially practice-changing treatment option, with ongoing discussions about the safety profiles and management of associated toxicities.

MARIPOSA publication in NEJM
FDA Press Release re: MARIPOSA

Trial Methodology

• Study Design: Phase III, randomized, multi-center trial
• Population: EGFR-mutated advanced NSCLC patients without previous systemic therapy
• Interventions: Comparison between amivantamab plus lazertinib and osimertinib (monotherapy)
• Endpoints: Primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety.
  

Detailed Results

• Progression-Free Survival (PFS): The combination of amivantamab and lazertinib demonstrated a significant improvement in PFS compared to osimertinib monotherapy. In patients with high-risk features (such as TP53 co-mutations, liver metastases, and detectable baseline ctDNA), the combination therapy was particularly effective.

• Overall Survival (OS): The MARIPOSA trial has reported an overall survival benefit of over 12 months.

  The MARIPOSA effect 🦋
  ‼️Awaited OS data for #Amivantamab + lazertinib vs osimertinib in 1L EGFRm advanced #lungcancer presented by Prof. James Yang at #ELCC25
  
  🎯OS HR 0.75 (95%CI: 0.61-0.92)
  🎉> 1 yr mOS advantage
  🚫no crossover allowed, ⬆️intracranial activity
  ⬇️toxicity… pic.twitter.com/MZlOq8xCsC

  — Dr. Estela Rodriguez (@Latinamd) March 27, 2025

• Safety and Tolerability: While the addition of lazertinib to amivantamab increased toxicity events such as skin disorders and infusion-related reactions, management strategies are being explored to mitigate these effects. 

Clinical Implications

The MARIPOSA trial underscores a potential shift in the standard of care, offering an improved therapeutic option for patients with EGFR-mutated NSCLC. The findings emphasize the importance of selecting appropriate patients who may benefit most from combination therapy, particularly those with high-risk disease profiles. Shared decision-making remains crucial in evaluating the benefit-risk profile of this regimen, considering both efficacy and potential adverse effects.

Key KOL Sentiments for MARIPOSA Trial