Sunvozertinib Granted FDA Accelerated Approval in EGFR Exon 20+ NSCLC

The FDA's approval of sunvozertinib is accompanied by the approval of a companion diagnostic test.

The FDA has given accelerated approval to sunvozertinib (Zegfrovy) for use in adult patients with locally advanced or metastatic non–small lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations following progression on platinum-based chemotherapy.¹

Along with this approval, the FDA announced its approval of a companion diagnostic test called Oncomine Dx Express Test to help identify EGFR exon 20 insertion mutations.

The approval of sunvozertinib is based on data from the multinational, open-label, dose randomization phase 2 WU-KONG1B trial (NCT03974022). The overall response rate (ORR) in patients taking sunvozertinib was 46% (95% CI, 35%-57%) and the duration of response (DOR) was 11.1 months (95% CI, 8.2-not evaluable [NE]).

Patients enrolled in WU-KONG1B had locally advanced/metastatic NSCLC with EGFR exon 20 insertion mutations whose diseased progressed after platinum-based chemotherapy. Patients evaluated (n = 85) were randomly assigned 1:1 to receive sunvozertinib at 200 mg daily or 300 mg daily. The recommended dose of sunvozertinib is 200 mg taken orally with food.

As noted in the FDA’s announcement, sunvozertinib’s prescribing information contains warnings for interstitial lung disease (ILD), pneumonitis, gastrointestinal adverse reactions, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.

Prior Findings on Sunvozertinib

The FDA granted priority review to sunvozertinib in the now approved indication in January based on previous findings from WU-KONG1B.

“Patients with [NSCLC with] EGFR [exon 20 insertion mutations] face a poor prognosis and limited treatment options,” Xiaolin Zhang, PhD, chief executive officer of Dizal, stated in a news release at that time.² “Sunvozertinib’s priority review designation marks an important regulatory milestone in Dizal’s efforts to address unmet medical needs worldwide. The results from the WU-KONG1 Part B study are promising. If approved, sunvozertinib as a single oral drug would offer a convenient and safe treatment option with superior efficacy for [patients with] NSCLC with EGFR [exon 20 insertion mutations].”

Data from the WU-KONG1B, which were presented at the 2024 ASCO Annual Meeting and had a cutoff date of March 22, 2024, showed that evaluable patients who received sunvozertinib at 300 mg once daily (n = 107) achieved a best ORR of 53.3% (97.5% CI, 42.0%-64.3%) and a confirmed ORR of 44.9% (97.5% CI, 34.0%-56.1%).³ Best responses included complete response (CR; 2.8%), confirmed CR (1.9%), partial response (PR; 50.5%), confirmed PR (43.0%), PR pending confirmation (3.7%) stable disease (36.4%), and progressive disease (7.5%). Three patients were not evaluable for response.

The most common grade 3 or higher treatment-related adverse effects (TRAEs) observed with the agent at the 300-mg dose included diarrhea (17.1%), increased blood creatinine phosphokinase levels (10.8%), anemia (3.6%), rash (3.6%), increased lipase levels (3.6%), decreased neutrophil counts (2.7%), hypokalemia (2.7%), decreased appetite (2.7%), and asthenia (2.7%). TRAEs led to dose reduction and treatment discontinuation in 36.0% and 6.3% of patients, respectively. Investigators noted that most of the common TRAEs were grade 1 or 2 in severity and clinically manageable. No TRAEs led to fatal outcomes.

Multiple trials are ongoing investigating the efficacy of sunvozertinib in NSCLC, including for rare mutations, in combination with anlotinib for co-mutations, for HER2 mutations, and combined with chemotherapy for use after EGFR-targeted tyrosine kinase inhibition.

Reference

1. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. FDA. July 2, 2025. Accessed July 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sunvozertinib-metastatic-non-small-cell-lung-cancer-egfr-exon-20
2. U.S. FDA granted priority review to Dizal’s sunvozertinib new drug application. News release. Dizal. January 7, 2025. Accessed January 7, 2025. https://www.dizalpharma.com/news/detail?id=84&search=&currentPage=1
3. Yang J CH, Doucet L, Wang M, et al. A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: primary analysis of WU-KONG1 study. J Clin Oncol. 2024;42(suppl 16)8513. doi:10.1200/JCO.2024.42.16_suppl.8513