FDA Grants Sunvozertinib Priority Review for Treatment of Non-Small Cell Lung Cancer With EGFR exon20ins Mutations

The new drug application for sunvozertinib (DZD9008; Dizal) was granted priority review by the FDA for treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) whose disease has progressed on or after platinum-based chemotherapy. If approved, sunvozertinib would offer patients a safe and convenient treatment option with superior efficacy.

Lung cancer | Image Credit: © David A Litman - stock.adobe.com

Sunvozertinib is an oral, irreversible EGFR inhibitor capable of targeting a broad spectrum of EGFR mutations with wild-type EGFR selectivity. It received accelerated approval in August of 2023 from the National Medical Products Administration of China, making it the world's first and only oral treatment for NSCLC patients with EGFR exon20ins. This decision was based on positive data from the WU-KONG6 study (NCT05712902), showing that sunvozertinib encouraged anti-tumor activity in patients with EGFR, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as human epidermal growth factor receptor 2 exon20ins.^1,2

In April 2024, the FDA granted breakthrough therapy designation to sunvozertinib followed by submission of a new drug application in November 2024. Both decisions are based on data from WU-KONG1 (NCT03974022), a part B, phase 2, multinational study investigating antitumor efficacy of sunvozertinib at 2 dose levels, 200 mg and 300 mg, in patients with platinum pre-treated NSCLC with EGFR exon20ins. Priority review of the NDA is also based on results from WU-KONG1.^3-6

The trial enrolled 184 patients who were randomized 1:1 to receive either 200 mg or 300 mg of sunvozertinib. According to the study results from part B, patients receiving 300 mg achieved an overall response rate of 53.3% (97.5% CI, 42.0%-64.3%) and a confirmed ORR of 44.9% (97.5% CI, 34.0%-56.1%).⁶

Additional and continued studies being conducted include WU-KONG1 part B and WU-KONG28 (NCT05668988), which are investigating sunvozertinib in the greater than or equal to second line and first line settings, respectively.⁷

"Patients with EGFR exon20ins NSCLC face a poor prognosis and limited treatment options," Xiaolin Zhang, PhD, CEO of Dizal, said in a news release. "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 NSCLC patients with EGFR exon20ins."¹

REFERENCES

1. US FDA granted priority review to Dizal's sunvozertinib new drug application. news release PR Newswire. January 7, 2025. Accessed January 7, 2025. https://www.prnewswire.com/news-releases/us-fda-granted-priority-review-to-dizals-sunvozertinib-new-drug-application-302344065.html

2. Sunvozertinib (DZD9008) in pretreated lung cancer patients with EGFR exon20 insertion mutation (WU-KONG6). Updated December 30, 2024. Accessed January 7, 2025. https://www.clinicaltrials.gov/study/NCT05712902

3. Scott R. FDA grants breakthrough therapy designation to first-line sunvozertinib for EGFR exon 20+ NSCLC. OncLive. April 8, 2024. Accessed January 7, 2025. https://www.onclive.com/view/fda-grants-breakthrough-therapy-designation-to-first-line-sunvozertinib-for-egfr-exon-20-nsclc

4. Ryan C. FDA approval sought for sunvozertinib in pretreated EGFR exon 20+ advanced NSCLC. OncLive. November 8, 2024. Accessed January 7, 2025. https://www.onclive.com/view/fda-approval-sought-for-sunvozertinib-in-pretreated-egfr-exon-20-advanced-nsclc

5. Assessing an oral EGFR inhibitor, sunvozertinib in patients who have advanced non-small cell lung cancer with EGFR or HER2 mutation (WU-KONG1). Updated December 12, 2024. Accessed January 7, 2025. https://www.clinicaltrials.gov/study/NCT03974022

6. Yang J, 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. May 29, 2024. doi:10.1200/JCO.2024.42.16_suppl.8513

7. A study of DZD9008 versus platinum-based doublet chemotherapy in local advanced or metastatic non-small cell lung cancer (WU-KONG28). Updated May 23, 2024. Accessed January 7, 2025. https://clinicaltrials.gov/study/NCT05668988