Amivantamab Emerges Positively from Its "Chrysalis"

Area of Science:

• Oncology
• Medical Genetics
• Pharmacology

Background:

• Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
• MET exon 14 skipping mutations are key oncogenic drivers in a subset of NSCLC patients.
• Targeted therapies are crucial for improving outcomes in NSCLC with specific genetic alterations.

Purpose of the Study:

• To evaluate the efficacy and safety of amivantamab in patients with NSCLC harboring MET exon 14 skipping mutations.
• To assess the combination therapy of amivantamab and lazertinib in pre-treated NSCLC patients.

Main Methods:

• Phase I CHRYSALIS trial assessing amivantamab monotherapy.
• Phase I/Ib CHRYSALIS-2 study evaluating amivantamab in combination with lazertinib.
• Response rates, progression-free survival, and overall survival were key endpoints.

Main Results:

• Amivantamab demonstrated a 33% overall response rate (ORR) and 6.7 months median progression-free survival (PFS) in the CHRYSALIS trial.
• In the CHRYSALIS-2 study, amivantamab plus lazertinib achieved a 33% ORR and 14.8 months median overall survival (OS) in osimertinib-resistant NSCLC.
• Encouraging efficacy was observed in both monotherapy and combination settings.

Conclusions:

• Amivantamab is an effective targeted therapy for NSCLC with MET exon 14 skipping mutations.
• Combination therapy with amivantamab and lazertinib shows potential for patients with advanced NSCLC previously treated with osimertinib.
• These findings support amivantamab as a valuable therapeutic option in specific NSCLC patient populations.