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

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-07-05 DOI:10.1016/j.canlet.2025.217904

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

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引用次数: 0

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.

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Sunvozertinib单药治疗EGFR外显子20插入突变NSCLC患者的疗效和安全性：一项2期单中心试验

目前，尚无无化疗疗法被批准用于EGFR外显子20插入突变（外显子20ins）的非小细胞肺癌（NSCLC）患者的一线治疗。Sunvozertinib是一种口服EGFR酪氨酸激酶抑制剂，已在中国被批准用于治疗≥二线EGFR外显子20ins的NSCLC。我们开展了sunvozertinib， WU-KONG15 （NCT05559645）的多组2期研究，以探索其在treatment-naïve EGFR外显子20ins NSCLC （Group 4）中的抗肿瘤疗效。给予Sunvozertinib 200mg，每日一次（QD）。主要终点为无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、缓解持续时间（DoR）、总生存期（OS）和安全性。探索终点包括循环肿瘤DNA （ctDNA）生物标志物。截至2025年1月15日，26例treatment-naïve EGFR外显子20ins NSCLC患者入组并纳入疗效分析集。中位PFS为10.1个月（95% CI: 6.2, 13.9），确诊ORR为73.1% (95% CI: 52.2, 88.4)，中位DoR为10.5个月（95% CI: 7.2, 21.2）。估计中位OS为23.1个月（95% CI: 13.1， NE）。共有99例患者被纳入安全性分析组。中位相对剂量强度为98.2%。≥3级治疗相关不良事件发生率为35.4%，包括血肌酸磷酸激酶升高（10.1%）、腹泻（8.1%）和贫血（8.1%）。血浆EGFR外显子20ins ctDNA阴性与更好的肿瘤反应相关。总之，sunvozertinib单药治疗在treatment-naïve EGFR外显子20蛋白NSCLC患者中表现出显著和持久的抗肿瘤疗效，并且耐受性良好，表明其有潜力成为一种有利的一线治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.