Efficacy and safety of sunvozertinib monotherapy as first-line treatment in NSCLC patients with EGFR exon 20 insertion mutations: A phase 2, single-center trial

Yan Xu; Minjiang Chen; Xiaoxing Gao; Xiaoyan Liu; Jing Zhao; Wei Zhong; Mei Wang; Hongli Lang; Chingwan Yip; Mengzhao Wang

doi:10.1016/j.canlet.2025.217904

Efficacy and safety of sunvozertinib monotherapy as first-line treatment in NSCLC patients with EGFR exon 20 insertion mutations: A phase 2, single-center trial

Cancer Lett. 2025 Jul 5:630:217904. doi: 10.1016/j.canlet.2025.217904. Online ahead of print.

Authors

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
² Dizal Pharmaceutical, China.
³ Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. Electronic address: mengzhaowang@sina.com.

PMID: 40618881
DOI: 10.1016/j.canlet.2025.217904

Abstract

Currently, no chemotherapy-free therapy is approved for the first-line treatment of non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations (exon20ins). Sunvozertinib is an oral EGFR tyrosine kinase inhibitor, which has been approved in China for ≥ second-line EGFR exon20ins NSCLC. We conducted a multi-group phase 2 study of sunvozertinib, WU-KONG15 (NCT05559645), to explore its antitumor efficacy in treatment-naïve EGFR exon20ins NSCLC (Group 4). Sunvozertinib was administered at 200 mg once daily (QD). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response (DoR), overall survival (OS), and safety. Exploratory endpoints included circulating tumor DNA (ctDNA) biomarkers. As of January 15, 2025, 26 treatment-naïve patients with EGFR exon20ins NSCLC were enrolled and included in the efficacy analysis set. The median PFS was 10.1 months (95 % CI: 6.2, 13.9), with confirmed ORR of 73.1 % (95 % CI: 52.2, 88.4) and median DoR of 10.5 months (95 % CI: 7.2, 21.2). The estimated median OS was 23.1 months (95 % CI: 13.1, NE). A total of 99 patients were included in the safety analysis set. The median relative dose intensity was 98.2 %. The incidence of Grade ≥3 treatment-related adverse events was 35.4 %, including blood creatine phosphokinase increased (10.1 %), diarrhoea (8.1 %) and anaemia (8.1 %). Negativity of plasma EGFR exon20ins ctDNA correlated with better tumor response. In conclusion, sunvozertinib monotherapy demonstrated significant and durable antitumor efficacy and was well-tolerated in treatment-naïve patients with EGFR exon20ins NSCLC, suggesting its potential as a favorable first-line treatment option.

Keywords: Biomarker; EGFR exon20ins; First-line; NSCLC; Sunvozertinib.