Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC

BACKGROUND: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

• Cho, B. C.
• Lu, S.
• Felip, E.
• Spira, A. I.
• Girard, N.
• Lee, J. S.
• Lee, S. H.
• Ostapenko, Y.
• Danchaivijitr, P.
• Liu, B.
• Alip, A.
• Korbenfeld, E.
• Mourão Dias, J.
• Besse, B.
• Lee, K. H.
• Xiong, H.
• How, S. H.
• Cheng, Y.
• Chang, G. C.
• Yoshioka, H.
• Yang, J. C.
• Thomas, M.
• Nguyen, D.
• Ou, S. I.
• Mukhedkar, S.
• Prabhash, K.
• D'Arcangelo, M.
• Alatorre-Alexander, J.
• Vázquez Limón, J. C.
• Alves, S.
• Stroyakovskiy, D.
• Peregudova, M.
• Şendur, M. A. N.
• Yazici, O.
• Califano, R.
• Guti
• de Marinis, F.
• Passaro, A.
• Kim, S. W.
• Gadgeel, S. M.
• Xie, J.
• Sun, T.
• Martinez, M.
• Ennis, M.
• Fennema, E.
• Daksh, M.
• Millington, D.
• Leconte, I.
• Iwasawa, R.
• Lorenzini, P.
• Baig, M.
• Shah, S.
• Bauml, J. M.
• Shreeve, S. M.
• Sethi, S.
• Knoblauch, R. E.
• Hayashi, H.