Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study
Natasha B. Leighl, Hiroaki Akamatsu, Sun Min Lim, Ying Cheng, Anna Minchom, Melina E. Marmarelis, Rachel E. Sanborn, James Chih‐Hsin Yang, Baogang Liu, Thomas John, Bartomeu Massutí, Alexander I. Spira, Se‐Hoon Lee, Jialei Wang, Juan Li, Caigang Liu, Silvia Novello, Masashi Kondo, Motohiro Tamiya, Ernesto Korbenfeld, Mor Moskovitz, Ji‐Youn Han, Mariam P. Alexander, Rohit Joshi, Enriqueta Felip, Pei Jye Voon, Pongwut Danchaivijitr, Ping‐Chih Hsu, Felipe José Silva Melo Cruz, Thomas Wehler, Laurent Greillier, Encarnação Teixeira, Danny Nguyen, Joshua K. Sabari, Angel Qin, Dariusz M. Kowalski, Mehmet Alı Nahıt Şendur, John Xie, Debopriya Ghosh, Ali Alhadab, Nahor Haddish‐Berhane, Pamela L. Clemens, Patricia Lorenzini, Remy B. Verheijen, Mohamed Gamil, Joshua Bauml, Mahadi Baig, Antonio Passaro, for the PALOMA-3 Investigators, Hiroaki Akamatsu, Mariam P. Alexander, Annalen Bleckmann, Federico Cappuzzo, Ying Cheng, Byoung Chul Cho, Timuçin Çil, Alexis B. Cortot, Pongwut Danchaivijitr, Till‐Oliver Emde, Dilek Erdem, Enriqueta Felip, F. Estevinho, Maria Lurdes Ferreira, Flavio Ferreira da Silva, Maria Campelo, Laurent Greillier, Alastair Greystoke, Ji‐Youn Han, Ping‐Chih Hsu, Jen‐Yu Hung, Mei Ji, Thomas John, Rohit Joshi, Young‐Chul Kim, Masashi Kondo, Ernesto Korbenfeld, Dariusz M. Kowalski, Se‐Hoon Lee, Natasha B. Leighl, Juan Li, Sheng-Hao Lin, Baogang Liu, Caigang Liu, John Seng-Hooi Low, Melina E. Marmarelis, Bartomeu Massutí, Anna R. Minchom, Sara Moore, Mor Moskovitz, Adnan Nagrial, Danny Nguyen, Silvia Novello, Y. Ohe, Mustafa Özgüroğlu, Özgür Özyılkan, Antonio Passaro, Nir Peled, Naiyarat Prasongsook, Angel Qin, Elisa F. Ramos
Abstract
PURPOSE Phase 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 METHODS Patients 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 (C trough ; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUC D1-D15 ). Key secondary end points were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory end point. RESULTS Overall, 418 patients underwent random assignment (subcutaneous group, n = 206; intravenous group, n = 212). Geometric mean ratios of C trough 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 AUC D1-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. CONCLUSION Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.