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
Authors: Leighl Natasha B. , Akamatsu Hiroaki , Lim Sun Min , Cheng Ying , Minchom Anna R. , Marmarelis Melina E. , Sanborn Rachel E. , Chih-Hsin Yang James , Liu Baogang , John Thomas , Massutí Bartomeu , Spira Alexander I. , Lee Se-Hoon , Wang Jialei , Li Juan , Liu Caigang , Novello Silvia , Kondo Masashi , Tamiya Motohiro , Korbenfeld Ernesto , Moskovitz Mor , Han Ji-Youn , Alexander Mariam , Joshi Rohit , Felip Enriqueta , Voon Pei Jye , Danchaivijitr Pongwut , Hsu Ping-Chih , Silva Melo Cruz Felipe José , Wehler Thomas , Greillier Laurent , Teixeira Encarnação , Nguyen Danny , Sabari Joshua K. , Qin Angel , Kowalski Dariusz , Şendur Mehmet Ali Nahit , Xie John , Ghosh Debopriya , Alhadab Ali , Haddish-Berhane Nahor , Clemens Pamela L. , Lorenzini Patricia , Verheijen Remy B. , Gamil Mohamed , Bauml Joshua M. , Baig Mahadi , Passaro Antonio ,   for the PALOMA-3 Investigators, Akamatsu Hiroaki , Alexander Mariam , Bleckmann Annalen , Cappuzzo Federico , Cheng Ying , Cho Byoung Chul , Cil Timucin , Cortot Alexis , Danchaivijitr Pongwut , Emde Till-Oliver , Erdem Dilek , Felip Enriqueta , Estevinho Fernanda , Lurdes Ferreira Maria , da Silva Flavio Ferreira , Garcia Campelo Maria del Rosario , Greillier Laurent , Greystoke Alastair , Han Ji-Youn , Hsu Ping-Chih , Hung Jen-Yu , Ji Mei , John Thomas , Joshi Rohit , Kim Young-Chul , Kondo Masashi , Korbenfeld Ernesto , Kowalski Dariusz , Lee Se-Hoon , Leighl Natasha , Li Juan , Lin Sheng-Hao , Liu Baogang , Liu Caigang , Seng-Hooi Low John , Marmarelis Melina E. , Massutí Bartomeu , Minchom Anna R. , Moore Sara , Moskovitz Mor , Nagrial Adnan , Nguyen Danny , Novello Silvia , Ohe Yuichiro , Özgüroğlu Mustafa , Ozyilkan Ozgur , Passaro Antonio , Peled Nir , Prasongsook Naiyarat , Qin Angel , Ramos Elisa F. , Sabari Joshua K. , Salinas Jorge , Sanborn Rachel E. , Sendur Mehmet Ali Nahit , José Silva Melo Cruz Felipe , Spira Alexander I. , Suksombooncharoen Thatthan , Tamiya Motohiro , Liang Tan Jiunn , Teixeira Encarnacao , Tota Rajanikar , Urban Damien , Vergnenègre Alain , Voon Pei Jye , Wainsztein Vanina , Wang Jialei , Wehler Thomas , Chih-Hsin Yang James , Yoshioka Hiroshige , Zer Alona , Zhao Yanqiu , Zurawski Bogdan 
Published: June 2024

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.