Multinational phase 3 trial of amivantamab plus chemotherapy for advanced non-small cell lung cancer with EGFR exon 20 insertions

Amivantamab is a bispecific EGFR and MET receptor-directed antibody. The multinational phase 3 PAPILLON trial assigned patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions who had not received previous systemic therapy 1:1 to receive amivantamab plus chemotherapy or chemotherapy alone. The primary outcome was progression-free survival. The median PFS was significantly longer in the amivatamab-chemotherapy group than in the chemotherapy alone group (11.4 versus 6.7 months; HR 0.40; p<0.001). At 18 months, progression-free survival was reported in 31% of patients in the amivantamab-chemotherapy group and 3% of patients in the chemotherapy alone group, while complete or partial response at data cutoff was reported in 73% and 47%, respectively (RR 1.50; p<0.001). The predominant adverse events with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab due to adverse effects. The authors conclude that addition of amivantamab to first-line chemotherapy for NSCLC with EGFR exon 20 insertions improved efficacy.