Efficacy and safety of sunvozertinib in treatment naïve NSCLC patients with EGFR exon20 insertion mutations.
Authors: Xu Yan , Yang James Chih-Hsin , Chiu Chao-Hua , Hsu Ping-Chih , Mitchell Paul , Chang Chia lun , John Tom , Bazhenova Lyudmila , Kim Tae Min , Yip Ching Wan , Wang Mengzhao , Janne Pasi A. , Zhou Caicun 
Published: June 2023

9073 Background: Sunvozertinib (DZD9008) is a rationally designed, irreversible EGFR inhibitor targeting EGFR mutations with wild-type EGFR selectivity. Two pivotal second line studies (WU-KONG1 [NCT03974022] and WU-KONG6 [NCT05712902 and CTR20211009]) are ongoing in NSCLC patients with EGFR exon20 insertion mutations (exon20ins). Primary analysis of WU-KONG6 study demonstrated promising efficacy and safety of sunvozertinib in ≥ second line setting. Herein, we reported preliminary results of sunvozertinib in the first line setting. Methods: Two ongoing studies WU-KONG1 and WU-KONG15 (NCT05559645) enrolled treatment naïve advanced NSCLC patients with EGFR exon20ins. WU-KONG1 is a multinational phase I/II study, and WU-KONG15 is an investigator-initiated phase II study in China. EGFR mutation status was confirmed by local or central testing using tissue or cytological samples. Sunvozertinib was administered orally until disease progression or other discontinuation criteria were met. Patients who had at least one post-treatment RECIST assessment by investigators were evaluable for efficacy analysis, and all patients who received at least one dose of sunvozertinib were included in the safety analysis. Results: As of January 15, 2023, a total of 36 treatment naïve advanced NSCLC patients with EGFR exon20ins received sunvozertinib daily dosing at RP2Ds. Median age was 66.5 years, and 63.9% (23/36) were female. The baseline ECOG PS was 0 or 1. Majority of patients (33/36, 91.7%) had metastatic diseases at study entry, with 22.2% (8/36) having > 3 metastatic sites and 22.2% (8/36) having baseline brain metastasis (BM). The most frequent mutation subtypes included 769_ASV (13/36, 36.1%), 770_SVD (2/36, 5.6%) and others (21/36, 58.3%). In 26 efficacy-evaluable patients, 19 patients showed tumor response, with a best objective response rate of 73.1%, among them 14 patients had confirmed response, and another 3 patients were still on treatment and pending confirmation. In patients with BM, tumor response was also observed intracranially. Median duration of response had not been reached by the data cut-off date. Safety findings were consistent with what was observed in previous studies of sunvozertinib. The most common treatment emergent adverse events (TEAEs) included diarrhea, CPK increase, and skin rash. The majority of adverse events were CTCAE grade 1 or 2 and manageable with supportive measures. Conclusions: Consistent with second line results, sunvozertinib demonstrated promising efficacy and safety profile as monotherapy in the first line setting for patients with advanced EGFR exon20ins NSCLC. The updated data will be presented at the conference. A phase III, multinational, randomized study (WU-KONG28, NCT05668988) is ongoing to compare sunvozertinib to chemotherapy as first line treatment for EGFR exon20ins NSCLC. Clinical trial information: NCT03974022 , NCT05559645 .