Leighl N.B.Akamatsu H.Lim S.M.Cheng Y.Minchom A.R.Marmarelis M.E.Sanborn R.E.Chih-Hsin Yang J.Liu B.John T.Massutí B.Spira A.I.Lee S.H.Wang J.Li J.Liu C.Novello S.Kondo M.Tamiya M.Korbenfeld E.Moskovitz M.Han J.Y.Alexander M.Joshi R.Felip E.Voon P.J.Danchaivijitr P.Hsu P.C.Silva Melo Cruz F.J.Wehler T.Greillier L.Teixeira E.Nguyen D.Sabari J.K.Qin A.Kowalski D.Nahit Şendur M.A.Xie J.Ghosh D.Alhadab A.Haddish-Berhane N.Clemens P.L.Lorenzini P.Verheijen R.B.Gamil M.Bauml J.M.Baig M.Passaro A.Mahidol University2024-09-282024-09-282024-01-01Journal of Clinical Oncology (2024)0732183Xhttps://repository.li.mahidol.ac.th/handle/123456789/101392PURPOSEPhase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy.PATIENTS AND METHODSPatients with EGFR-mutated advanced NSCLC who progressed after osimertinib and platinum-based chemotherapy were randomly assigned 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Coprimary pharmacokinetic noninferiority end points were trough concentrations (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-D15). Key secondary end points were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory end point.RESULTSOverall, 418 patients underwent random assignment (subcutaneous group, n = 206; intravenous group, n = 212). Geometric mean ratios of Ctrough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04 to 1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27 to 1.61) at cycle-4-day-1; the cycle-2 AUCD1-D15 was 1.03 (90% CI, 0.98 to 1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42 to 0.92; nominal P =.02). Fewer patients in the subcutaneous group experienced infusion-related reactions (IRRs; 13% v 66%) and venous thromboembolism (9% v 14%) versus the intravenous group. Median administration time for the first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab and to 5 hours (range, 0.2-9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; the end-of-treatment rates were 85% and 35%, respectively.CONCLUSIONSubcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.Biochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1200/JCO.24.010012-s2.0-852010128551527775538857463