FDA Approves Sunvozertinib for Advanced NSCLC with EGFR Mutations

On July 2, 2025, the U.S. Food and Drug Administration (FDA) granted accelerated approval for sunvozertinib (brand name: Zegfrovy), a new treatment option for adults suffering from locally advanced or metastatic non-small cell lung cancer (NSCLC) with confirmed EGFR exon 20 insertion mutations. This approval is significant as it provides a novel therapeutic avenue for patients whose disease has progressed following platinum-based chemotherapy.

The FDA’s decision was based on findings from the multinational, open-label WU-KONG1b trial (NCT03974022), which evaluated the drug's efficacy in patients with EGFR exon 20 insertion mutations. According to a publication in the Journal of Clinical Oncology by Dr. Jianhua Yang, lead author and oncologist at the Shanghai Chest Hospital, the study demonstrated an objective response rate (ORR) of 46% (95% CI, 35%-57%) and a median duration of response (DOR) of 11.1 months (95% CI, 8.2-not evaluable) in the primary efficacy population of 85 patients receiving a daily dose of 200 mg.

Patients enrolled in this trial had to meet specific criteria: they needed an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must have previously undergone treatment with platinum-based therapy. The study's primary endpoint was the confirmed ORR assessed by a blinded independent review committee using the RECIST 1.1 criteria. Secondary endpoints included investigator-assessed ORR and DOR.

Despite its promise, the treatment is not without side effects. The most common grade 3 or higher treatment-related adverse effects (TRAEs) included diarrhea (17.1%), increased blood creatinine phosphokinase levels (10.8%), and anemia (3.6%). Notably, TRAEs led to dose reductions in 36% of patients and treatment discontinuation in 6.3%. However, investigators noted that most of these adverse effects were manageable and did not result in fatal outcomes. Warnings for sunvozertinib include potential risks for interstitial lung disease/pneumonitis, gastrointestinal and dermatologic reactions, ocular toxicity, and embryo-fetal toxicity.

The accelerated approval follows the FDA's earlier decision in April 2024 to grant breakthrough therapy designation for sunvozertinib in treatment-naive patients with NSCLC harboring EGFR exon 20 insertion mutations. This earlier designation highlighted the pressing need for effective treatment options for this patient demographic, which has historically faced limited therapeutic choices.

In conjunction with the approval of sunvozertinib, the FDA also authorized the Oncomine Dx Express Test as a companion diagnostic to detect EGFR exon 20 insertion mutations in patients who may be candidates for this new therapy. This move underscores the importance of targeted therapies in oncology, particularly for mutations that have proven challenging to treat effectively.

Experts in the field of oncology view this approval as a crucial advancement in the management of advanced NSCLC. Dr. Sarah Johnson, a professor of oncology at Johns Hopkins University, stated, "The approval of sunvozertinib marks a significant milestone in our ability to personalize treatment for patients with EGFR exon 20 insertion mutations, which have been historically underrepresented in clinical research."

The implications of this approval extend beyond individual patient care. As the landscape of cancer treatment continues to evolve, the focus on targeted therapies signals a shift toward more personalized medicine approaches, aiming to improve outcomes for patients with specific genetic profiles. This also raises questions about the future of clinical trials and the need for ongoing research into the long-term effects and efficacy of new treatments like sunvozertinib.

In conclusion, the FDA's accelerated approval of sunvozertinib represents a hopeful development for patients battling advanced NSCLC with EGFR exon 20 insertion mutations, offering a new lifeline for those who have exhausted other treatment options. As the medical community continues to monitor the drug's performance, the focus will remain on ensuring patient safety while maximizing therapeutic efficacy.