Amivantamab Treatment for EGFR Exon 20 Insertion NSCLC

Introduction to Amivantamab Trials

• The National Comprehensive Cancer Network (NCCN) recommends amivantamab plus carboplatin-pemetrexed as a Category 1 and preferred first-line treatment option for advanced or metastatic nonsquamous EGFR exon 20 insertion mutation-positive NSCLC 1, 2, 3, 4

PAPILLON Trial Results

• In the PAPILLON trial, a Phase III randomized trial comparing amivantamab plus carboplatin-pemetrexed versus chemotherapy alone in 308 treatment-naïve patients with advanced NSCLC harboring EGFR exon 20 insertions, the median PFS was 11.4 months (amivantamab-chemotherapy) vs 6.7 months (chemotherapy alone); HR 0.40, P < 0.001 1, 2, 3, 4
• The interim OS analysis showed HR 0.67 (P = 0.11) 1, 2, 3, 4

CHRYSALIS Trial Results

• In the CHRYSALIS trial, a Phase I study evaluating amivantamab monotherapy in 81 patients with EGFR exon 20 insertion-positive metastatic NSCLC who had received one or more prior lines of therapy, the overall response rate was 40% (including 3 complete responses) 1, 3, 4, 5
• The median PFS was 8.3 months 1, 3, 4, 5

Regulatory Impact and Safety Profile

• Amivantamab-vmjw received FDA approval as monotherapy for adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertions whose disease progressed on or after platinum-based chemotherapy 1, 3, 4, 5
• Common treatment-related adverse events included cutaneous reactions, infusion-related reactions, and paronychia 1, 3, 4, 5
• Most common grade 3-4 adverse events: hypokalemia, pulmonary embolism, neutropenia, diarrhea, and rash 1, 3, 4, 5