TY - JOUR
T1 - Amivantamab Plus Lazertinib in Atypical EGFR -Mutated Advanced Non-Small Cell Lung Cancer :
T2 - Results From CHRYSALIS-2
AU - Tomasini, Pascale
AU - Wang, Yongsheng
AU - Li, Yongsheng
AU - Felip, Enriqueta
AU - Wu, Lin
AU - Cui, Jiuwei
AU - Besse, Benjamin
AU - Spira, Alexander I.
AU - Neal, Joel W.
AU - Goto, Koichi
AU - Baik, Christina
AU - Marmarelis, Melina E.
AU - Ichihara, Eiki
AU - Zhang, Yiping
AU - Lee, Jong-Seok
AU - Lee, Se-Hoon
AU - Chih-Hsin Yang, James
AU - Michels, Sebastian
AU - Anastasiou, Zacharias
AU - Curtin, Joshua C
AU - Lyu, Xuesong
AU - Mahoney, Janine
AU - Demirdjian, Levon
AU - Meyer, Craig S.
AU - Zhang, Youyi
AU - Leconte, Isabelle
AU - Lorenzini, Patricia
AU - Knoblauch, Roland E.
AU - Trani, Leonardo
AU - Baig, Mahadi
AU - Bauml, Joshua M.
AU - Cho, Byoung Chul
PY - 2025
Y1 - 2025
N2 - For patients with advanced non-small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited. CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR). As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively. In participants with atypical EGFR -mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.
AB - For patients with advanced non-small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited. CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR). As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively. In participants with atypical EGFR -mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.
U2 - 10.1200/JCO-24-02835
DO - 10.1200/JCO-24-02835
M3 - Article
C2 - 41325571
SN - 0732-183X
VL - 44
SP - 54
EP - 65
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 1
ER -
ODS 3: Salud y bienestar