FDA Grants Accelerated Approval to Sunvozertinib for Metastatic NSCLC With EGFR Exon 20 Insertion Mutations

FDA

The FDA has granted accelerated approval to sunvozertinib (Zegfrovy) for the treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or following platinum-based chemotherapy.1

The efficacy of the agent was examined in the multinational, open-label WU-KONG1b trial (NCT03974022). Data showed that sunvozertinib elicited an objective response rate (ORR) of 46% (95% CI, 35%-57%), with a duration of response (DOR) of 11.1 months (95% CI, 8.2-not evaluable).

About the Trial

WU-KONG1 Part B enrolled patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations confirmed in tumor tissue.2 Patients needed to have an ECOG performance status of 0 or 1 and have received prior treatment with platinum-based chemotherapy.

Patients were randomly assigned 1:1 to receive sunvozertinib at 200 mg daily or 300 mg daily. The primary efficacy population comprised 85 patients who received the agent at the 200-mg dose once daily until progressive disease or unacceptable toxicity.1

The trial's primary end point was confirmed ORR by blinded independent review committee (IRC) assessment and RECIST 1.1 criteria; IRC-assessed DOR served as a key secondary end point.2 Other secondary end points included investigator-assessed ORR and DOR.

Safety Spotlight

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%).2

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.

Prescribing information for the drug includes warnings and precautions for interstitial lung disease/pneumonitis, gastrointestinal adverse reactions, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.1

What Came Before

Previously, in April 2024, the FDA granted breakthrough therapy designation to sunvozertinib for patients with treatment-naive NSCLC harboring an EGFR exon 20 insertion mutation.3

Also Approved

The regulatory agency also cleared the Oncomine Dx Express Test for use as a companion diagnostic device to detect EGFR exon 20 insertion mutations in patients with NSCLC who may be candidates for sunvozertinib.1

References

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. 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
3. FDA grants breakthrough therapy designation to sunvozertinib for the first-line treatment of patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations. News Release. Dizal Pharma. April 7, 2024. Accessed July 2, 2025. https://www.dizalpharma.com/news/detail?id=70&search=&currentPage=1