Amivantamab Plus Lazertinib in Atypical -Mutated Advanced Non-Small Cell Lung Cancer: Results From CHRYSALIS-2.
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Journal Volume
44
Journal Issue
1
Start Page
54
End Page
65
ISSN
1527-7755
Date Issued
2026-01
Author(s)
Tomasini, Pascale
Wang, Yongsheng
Li, Yongsheng
Felip, Enriqueta
Wu, Lin
Cui, Jiuwei
Besse, Benjamin
Spira, Alexander I
Neal, Joel W
Goto, Koichi
Baik, Christina S
Marmarelis, Melina E
Ichihara, Eiki
Zhang, Yiping
Lee, Jong-Seok
Lee, Se-Hoon
Michels, Sebastian
Anastasiou, Zacharias
Curtin, Joshua C
Lyu, Xuesong
Mahoney, Janine
Demirdjian, Levon
Meyer, Craig S
Zhang, Youyi
Leconte, Isabelle
Lorenzini, Patricia
Knoblauch, Roland E
Trani, Leonardo
Baig, Mahadi
Bauml, Joshua M
Cho, Byoung Chul
Abstract
For patients with advanced non-small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor () mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited.
CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical 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 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 -mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.
SDGs
Type
journal article