Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation

Yan Xu; James Chih Hsin Yang; Yanqiu Zhao; Ludovic Doucet; Jianying Zhou; Yongsheng Wang; David Planchard; Yun Fan; Bo Jin; Zhigang Han; Laurent Greillier; Julien Mazieres; Meili Sun; Ying Hu; Xia Song; Cuimin Ding; Lin Wu; Kejing Tang; Li Liang; Yu Yao; Ying Cheng; Yong He; Bruna Pellini Ferreira; François Ghiringhelli; Enriqueta Felip; Joaquim Bosch-Barrera; Anwen Liu; Yan Yu; Xiaorong Dong; Junzhen Gao; D. Ross Camidge; Weiqi Nian; Chengzhi Zhou; Runxiang Yang; Thomas John; Bo Gao; Lyudmila Bazhenova; Misako Nagasaka; Jianghong Wang; Xiubao Ren; Fei Xu; Wen Li; Dahai Zhao; Huijie Wang; Si Sun; Jian'an Huang; Xuehua Zhu; Li Zheng; Pasi A. Jänne; Mengzhao Wang

doi:10.1016/j.xcrm.2025.102121

Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation

Yan Xu, James Chih Hsin Yang, Yanqiu Zhao, Ludovic Doucet, Jianying Zhou, Yongsheng Wang, David Planchard, Yun Fan, Bo Jin, Zhigang Han, Laurent Greillier, Julien Mazieres, Meili Sun, Ying Hu, Xia Song, Cuimin Ding, Lin Wu, Kejing Tang, Li Liang, Yu YaoYing Cheng, Yong He, Bruna Pellini Ferreira, François Ghiringhelli, Enriqueta Felip, Joaquim Bosch-Barrera, Anwen Liu, Yan Yu, Xiaorong Dong, Junzhen Gao, D. Ross Camidge, Weiqi Nian, Chengzhi Zhou, Runxiang Yang, Thomas John, Bo Gao, Lyudmila Bazhenova, Misako Nagasaka, Jianghong Wang, Xiubao Ren, Fei Xu, Wen Li, Dahai Zhao, Huijie Wang, Si Sun, Jian'an Huang, Xuehua Zhu, Li Zheng, Pasi A. Jänne, Mengzhao Wang

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Résumé

This is a report of biomarker analysis for sunvozertinib, a leading epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutation (exon20ins) non-small cell lung cancer (NSCLC). There is a positive correlation between positive EGFR exon20ins in plasma circulating tumor DNA (ctDNA) and advanced disease. Shorter progression-free survival and lower objective response rate (45.8% vs. 68.0%) were observed in patients with positive EGFR exon20ins compared to those with negative status. Droplet digital PCR analysis showed that the EGFR exon20ins allele in ctDNA decreased over time in 85.7% of patients, with the earliest clearance occurred after 1 week of sunvozertinib treatment. Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib.

langue originale	Anglais
Numéro d'article	102121
journal	Cell Reports Medicine
Volume	6
Numéro de publication	5
Les DOIs	https://doi.org/10.1016/j.xcrm.2025.102121
état	Publié - 20 mai 2025

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10.1016/j.xcrm.2025.102121

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Xu, Y., Yang, J. C. H., Zhao, Y., Doucet, L., Zhou, J., Wang, Y., Planchard, D., Fan, Y., Jin, B., Han, Z., Greillier, L., Mazieres, J., Sun, M., Hu, Y., Song, X., Ding, C., Wu, L., Tang, K., Liang, L., ... Wang, M. (2025). Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation. Cell Reports Medicine, 6(5), Article 102121. https://doi.org/10.1016/j.xcrm.2025.102121

@article{86ff075288184e8f8fce25669e85660b,

title = "Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation",

abstract = "This is a report of biomarker analysis for sunvozertinib, a leading epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutation (exon20ins) non-small cell lung cancer (NSCLC). There is a positive correlation between positive EGFR exon20ins in plasma circulating tumor DNA (ctDNA) and advanced disease. Shorter progression-free survival and lower objective response rate (45.8% vs. 68.0%) were observed in patients with positive EGFR exon20ins compared to those with negative status. Droplet digital PCR analysis showed that the EGFR exon20ins allele in ctDNA decreased over time in 85.7% of patients, with the earliest clearance occurred after 1 week of sunvozertinib treatment. Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib.",

keywords = "EGFR exon20ins, NSCLC, biomarker, sunvozertinib",

author = "Yan Xu and Yang, {James Chih Hsin} and Yanqiu Zhao and Ludovic Doucet and Jianying Zhou and Yongsheng Wang and David Planchard and Yun Fan and Bo Jin and Zhigang Han and Laurent Greillier and Julien Mazieres and Meili Sun and Ying Hu and Xia Song and Cuimin Ding and Lin Wu and Kejing Tang and Li Liang and Yu Yao and Ying Cheng and Yong He and Ferreira, {Bruna Pellini} and Fran{\c c}ois Ghiringhelli and Enriqueta Felip and Joaquim Bosch-Barrera and Anwen Liu and Yan Yu and Xiaorong Dong and Junzhen Gao and Camidge, {D. Ross} and Weiqi Nian and Chengzhi Zhou and Runxiang Yang and Thomas John and Bo Gao and Lyudmila Bazhenova and Misako Nagasaka and Jianghong Wang and Xiubao Ren and Fei Xu and Wen Li and Dahai Zhao and Huijie Wang and Si Sun and Jian'an Huang and Xuehua Zhu and Li Zheng and J{\"a}nne, {Pasi A.} and Mengzhao Wang",

note = "Publisher Copyright: {\textcopyright} 2025",

year = "2025",

month = may,

day = "20",

doi = "10.1016/j.xcrm.2025.102121",

language = "English",

volume = "6",

journal = "Cell Reports Medicine",

issn = "2666-3791",

number = "5",

}

Xu, Y, Yang, JCH, Zhao, Y, Doucet, L, Zhou, J, Wang, Y, Planchard, D, Fan, Y, Jin, B, Han, Z, Greillier, L, Mazieres, J, Sun, M, Hu, Y, Song, X, Ding, C, Wu, L, Tang, K, Liang, L, Yao, Y, Cheng, Y, He, Y, Ferreira, BP, Ghiringhelli, F, Felip, E, Bosch-Barrera, J, Liu, A, Yu, Y, Dong, X, Gao, J, Camidge, DR, Nian, W, Zhou, C, Yang, R, John, T, Gao, B, Bazhenova, L, Nagasaka, M, Wang, J, Ren, X, Xu, F, Li, W, Zhao, D, Wang, H, Sun, S, Huang, J, Zhu, X, Zheng, L, Jänne, PA & Wang, M 2025, 'Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation', Cell Reports Medicine, VOL. 6, Numéro 5, 102121. https://doi.org/10.1016/j.xcrm.2025.102121

TY - JOUR

T1 - Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation

AU - Xu, Yan

AU - Yang, James Chih Hsin

AU - Zhao, Yanqiu

AU - Doucet, Ludovic

AU - Zhou, Jianying

AU - Wang, Yongsheng

AU - Planchard, David

AU - Fan, Yun

AU - Jin, Bo

AU - Han, Zhigang

AU - Greillier, Laurent

AU - Mazieres, Julien

AU - Sun, Meili

AU - Hu, Ying

AU - Song, Xia

AU - Ding, Cuimin

AU - Wu, Lin

AU - Tang, Kejing

AU - Liang, Li

AU - Yao, Yu

AU - Cheng, Ying

AU - He, Yong

AU - Ferreira, Bruna Pellini

AU - Ghiringhelli, François

AU - Felip, Enriqueta

AU - Bosch-Barrera, Joaquim

AU - Liu, Anwen

AU - Yu, Yan

AU - Dong, Xiaorong

AU - Gao, Junzhen

AU - Camidge, D. Ross

AU - Nian, Weiqi

AU - Zhou, Chengzhi

AU - Yang, Runxiang

AU - John, Thomas

AU - Gao, Bo

AU - Bazhenova, Lyudmila

AU - Nagasaka, Misako

AU - Wang, Jianghong

AU - Ren, Xiubao

AU - Xu, Fei

AU - Li, Wen

AU - Zhao, Dahai

AU - Wang, Huijie

AU - Sun, Si

AU - Huang, Jian'an

AU - Zhu, Xuehua

AU - Zheng, Li

AU - Jänne, Pasi A.

AU - Wang, Mengzhao

PY - 2025/5/20

Y1 - 2025/5/20

N2 - This is a report of biomarker analysis for sunvozertinib, a leading epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutation (exon20ins) non-small cell lung cancer (NSCLC). There is a positive correlation between positive EGFR exon20ins in plasma circulating tumor DNA (ctDNA) and advanced disease. Shorter progression-free survival and lower objective response rate (45.8% vs. 68.0%) were observed in patients with positive EGFR exon20ins compared to those with negative status. Droplet digital PCR analysis showed that the EGFR exon20ins allele in ctDNA decreased over time in 85.7% of patients, with the earliest clearance occurred after 1 week of sunvozertinib treatment. Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib.

AB - This is a report of biomarker analysis for sunvozertinib, a leading epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion mutation (exon20ins) non-small cell lung cancer (NSCLC). There is a positive correlation between positive EGFR exon20ins in plasma circulating tumor DNA (ctDNA) and advanced disease. Shorter progression-free survival and lower objective response rate (45.8% vs. 68.0%) were observed in patients with positive EGFR exon20ins compared to those with negative status. Droplet digital PCR analysis showed that the EGFR exon20ins allele in ctDNA decreased over time in 85.7% of patients, with the earliest clearance occurred after 1 week of sunvozertinib treatment. Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib.

KW - EGFR exon20ins

KW - NSCLC

KW - biomarker

KW - sunvozertinib

UR - http://www.scopus.com/inward/record.url?scp=105004352939&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2025.102121

DO - 10.1016/j.xcrm.2025.102121

M3 - Article

AN - SCOPUS:105004352939

SN - 2666-3791

VL - 6

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 5

M1 - 102121

ER -