Sunvozertinib Approved by FDA as Oral Treatment of NSCLC With EGFR Exon 20 Insertion Mutations

The FDA has granted accelerated approval to sunvozertinib (Zegfrovy; Dizal), an irreversible epidermal growth factor receptor (EGFR) inhibitor, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations (exon20ins) whose disease has progressed on or following platinum-based chemotherapy, according to a news release from Dizal.¹

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Sunvozertinib Fills Treatment Gap for Patients With EGFR exon20ins

With this approval, sunvozertinib becomes the first and only approved, targeted oral treatment for patients with NSCLC and EGFR exon20ins. Detection of NSCLC impacted by EGFR exon20ins can be completed using the Thermo Fisher Scientific’s Oncomine Dx Express Test, a next-generation sequencing companion diagnostic for sunvozertinib, which was simultaneously approved by the FDA. The test can deliver results in as little as 24 hours to better inform treatment protocol with sunvozertinib in patients with EGFR exon20ins.¹

Sunvozertinib was previously granted priority review by the FDA in this indication. It was also granted breakthrough therapy designation, helping to facilitate the approval and development process of the EGFR inhibitor. Sunvozertinib now has the potential to further bolster the treatment paradigm for patients with NSCLC, especially those with EGFR exon20ins, who have a lack of available treatment options.²

“As the world's only approved targeted oral therapy for EGFR exon20ins NSCLC, [sunvozertinib] has expanded the treatment paradigm in this therapeutic area that has long lacked convenient and effective treatment options,” Pasi A. Jänne, MD, PhD, Dana-Farber Cancer Institute of Harvard Medical School and principal investigator of WU-KONG1B, said in the news release. “Its convenient once-daily oral dosing substantially improves administration convenience and patient adherence, which is an increasingly critical factor as lung cancer care shifts toward chronic disease management.”¹

Data From WU-KONG1 Part B Demonstrate Efficacy and Safety of Sunvozertinib

Approval of sunvozertinib was based in part on the positive results from the multinational, pivotal phase WU-KONG1 Part B study (WU-KONG1B; NCT03974022). The results, presented by investigators as an oral presentation at the 2024 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology, indicate promising antitumor activity and a tolerable safety profile in patients with platinum-pretreated NSCLC with EGFR exon20ins.^3,4

WU-KONG1B assessed the efficacy of sunvozertinib at 200-mg and 300-mg dose levels. A total of 184 patients were randomized to receive either dose of sunvozertinib, with end points including tumor response, duration of response (DoR), progression-free survival (PFS), overall response rate (ORR), and complete response (CR).³

The investigators found that, per assessment by an Independent Review Committee, the best ORR was 54.3% (41.0% confirmed, 5.8% pending confirmation), while a confirmed complete response was observed in 2.9% of patients. Importantly, the disease control rate (which includes CR, partial response, and stable disease rates) was 90.8% across the population.³

In a significant development, the primary end point met its predefined target with statistical significance, as tumor responses were observed in patients across cohorts, including those with baseline brain metastasis, varying demographics, and differing EGFR exon20ins subtypes, according to the investigators. Positively, at a median follow-up of 5.5 months for responders, DoR was not reached, with 74.6% of responders sustaining their response. Furthermore, PFS data was not mature at approximately 6 months follow-up.³

Future Evaluations

Safety was comparable to previously reported results of sunvozertinib, with the most common drug-related treatment-emergent adverse events (TEAEs) including diarrhea and skin rash. A majority of these TEAEs were clinically manageable and of grade 1 or 2 severity, a promising development for both patients and providers.³

Sunvozertinib is set to be evaluated further in the phase 3 WU-KONG28 study, which will compare the treatment with platinum-based doublet chemotherapies in treatment-naïve patients with NSCLC harboring EGFR exon20ins. The trial will take place across 16 countries and regions, according to Dizal. Based on the promising results from the WU-KONG1B trial and previously garnered data indicating positive PFS and ORR with sunvozertinib in the first-line setting as a single oral agent, the drug is poised to revolutionize the treatment landscape for NSCLC.¹

“In NSCLC, EGFR exon20ins represent the third most common type of EGFR mutation. EGFR exon20ins are particularly challenging to treat due to their unique spatial conformation, diverse mutation subtypes, and high heterogeneity. As a result, patients face a poor prognosis and limited treatment options,” Mengzhao Wang, MD, PhD, principal investigator of WU-KONG1B at Peking Union Medical College Hospital, said in the news release. "The US approval of [sunvozertinib] will enable more patients around the world to benefit from this drug.”¹

REFERENCES

1. Dizal. Dizal’s ZEGFROVY (sunvozertinib) receives FDA accelerated approval as the only targeted oral treatment for non-small cell lung cancer with EGFR exon 20 insertion mutations. News Release. Released July 3, 2025. Accessed July 7, 2025. https://www.dizalpharma.com/news/detail?id=95&search=&currentPage=1

2. Gerlach A. FDA grants sunvozertinib priority review for treatment of non-small cell lung cancer with EGFR exon20ins mutations. Pharmacy Times. Published January 7, 2025. Accessed July 7, 2025. https://www.pharmacytimes.com/view/fda-grants-sunvozertinib-priority-review-for-treatment-of-non-small-cell-lung-cancer-with-egfr-exon20ins-mutations

3. Yang JC, 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(16). doi:10.1200/JCO.2024.42.16_suppl.851

4. Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer with EGFR or HER2 Mutation (WU-KONG1). National Library of Medicine. ClinicalTrials.gov Identifier: NCT03974022. Last Updated February 28, 2025. Accessed July 7, 2025. https://www.clinicaltrials.gov/study/NCT03974022