Multinational phase 3 trial of lazertinib plus subcutaneous versus intravenous amivantamab for refractory EGFR-mutated aNSCLC

The multinational phase 3 PALOMA-3 study compared subcutaneous versus intravenous amivantamab, both in combination with lazertinib, for EGFR-mutated advanced NSCLC progressing after osimertinib and platinum-based chemotherapy. Pharmacokinetic analyses showed noninferiority of the subcutaneous administration. In the subcutaneous verus the intravenous group the median overall survival was longer (HR 0.62; p=0.02), infusion-related reactions were reduced (13% versus 66%), venous thromboembolism was reduced (9% versus 14%), median time for first administration was reduced (4.8 minutes versus 5 hours), and patient-reported convenience was higher (first administration 85% versus 52%; end-of-treatment 85% versus 35%). The authors conclude that subcutaneous amivantanab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offerering a consistent safety profile with reduced infusion-related reaction, increased convenience, and prolonged survival.