FDA Grants Priority Review to Sunvozertinib for EGFR exon20 NSCLC

The WU-KONG1 trial found that sunvozertinib yielded a best ORR of 53.3% and a cORR of 44.9% in patients with NSCLC harboring EGFR exon20ins mutations.

The FDA has accepted and granted priority review to a new drug application (NDA) for sunvozertinib (DZD9008), an oral EGFR inhibitor, in the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who also have EGFR exon 20 insertion mutations (exon20ins) and whose disease has progressed on or after platinum-based chemotherapy, according to a press release from the developer, Dizal.¹

The NDA was submitted in November 2024.² Previously, sunvozertinib received the FDA breakthrough therapy designation in the same patient population in April 2024.³ Additionally, in 2023, the National Medical Products Administration of China granted sunvozertinib accelerated approval, which made the drug the first and only oral treatment for the indicated population.

Data from the dose-extension part (part B) of the open-label phase 1/2 WU-KONG1 study (NCT03974022) that investigated sunvozertinib in relapsed or refractory patients with NSCLC who also have EGFR exon20ins—which supported the NDA submission—were presented at the 2024 American Society of Clinical Oncology Annual Meeting (ASCO).

“Patients with EGFR exon20ins NSCLC [have] a poor prognosis and limited treatment options," Xiaolin Zhang, PhD, chief executive officer of Dizal, said in the news release.¹ "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 exon20ins."

In the trial, the best overall response rate (ORR) was 53.3% (97.5% CI, 42.0%-64.3%), and the confirmed ORR was 44.9% (97.5% CI, 34.0%-56.1%). Complete responses (CRs) were observed in 3 patients (2.8%), confirmed CRs in 2 (1.9%); partial responses (PRs) were observed in 54 patients (50.5%), confirmed PRs in 46 (43.0%), and PRs pending confirmation in 4 (3.7%). Stable disease occurred in 39 patients (36.4%) while progressive disease occurred in 8 (7.5%); 3 patients (2.8%) were not evaluable. Furthermore, efficacy was observed regardless of amivantamab-vmjw (Rybrevant) treatment; in patients with or without amivantamab treatment, the best ORRs were 50% and 53.8%, respectively.

The 9-month duration of response (DOR) rate was 57%, and median DOR was not reached at the time of presentation.

Regarding safety, the most common treatment-related adverse events (TRAEs) of grade 3 of higher were diarrhea (17.1%), blood creatine phosphokinase increases (10.8%), anemia (3.6%), rash (3.6%), and lipase increases (3.6%). Additionally, 36.0% and 6.3% of patients experienced dose reduction and treatment discontinuation, respectively. There were no TRAEs with fatal outcomes.

A total of 107 patients were included in the analysis, and all were administered 300 mg of sunvozertinib orally once daily. Administration continued until discontinuation criteria were met.

The median age was 64.0 (range, 37-85), 37 patients (34.6%) reported being a current or former smoker, 27 (25.2%) had brain metastasis at baseline, 104 (97.2%) had metastatic disease and the remaining 3 (2.8%) had locally advanced disease. Additionally, 68 patients (63.6%) received less than 2 prior lines of therapy, and 39 (36.4%) received 2 or more; 107 received platinum-based chemotherapy (100.0%), 52 (48.6%) received onco-immunotherapy, 30 (28.0%) received antiangiogenic therapy, 14 (13.1%) received amivantamab, 14 (13.1%) received an EGFR tyrosine kinase inhibitor, and 6 (5.6%) received other forms of treatment.

Eligible patients had locally advanced or metastatic NSCLC with EGFR exon20ins in tumor tissues confirmed via local or sponsor-designated laboratory testing, an ECOG performance status of 0 or 1, and a history of prior treatment with platinum-based chemotherapy.

The trial’s primary end point was ORR assessed by an independent review committee (IRC). Secondary end points include DOR by IRC evaluation, investigator-assessed ORR, and investigator-assessed DOR.

Currently, the phase 3, randomized, multinational WU-KONG28 trial (NCT05668988) is evaluating the efficacy and safety of sunvozertinib compared with platinum-based chemotherapy in the first-line treatment of patients with NSCLC also harboring EGFR exon20ins.

References

1. U.S. FDA granted priority review to Dizal's sunvozertinib new drug application. News release. Dizal Pharmaceutical. January 7, 2025. Accessed January 7, 2025. https://tinyurl.com/59syffnb
2. Dizal submits new drug application to the U.S. FDA for sunvozertinib in treating relapsed or refractory non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. Dizal. November 8, 2024. Accessed January 7, 2025. https://tinyurl.com/2x5hnkwa
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. April 7, 2024. Accessed January 7, 2025. https://tinyurl.com/yjy8jhm4
4. Yang JC-H, 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