Frontline Sunvozertinib Improves PFS vs Chemotherapy in EGFR+ NSCLC

First-line sunvozertinib (Zegfrovy) monotherapy demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) improvement vs platinum-based chemotherapy among patients with non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, according to a press release on topline findings from the phase 3 WU-KONG28 trial (NCT05668988).¹

The investigational agent also showed improvements vs chemotherapy across all secondary end points, which included confirmed overall response rate (ORR), duration of response (DOR), and disease control rate (DCR). Additionally, treatment with sunvozertinib was typically well tolerated, and the agent’s safety profile as comparable with previous reports.

Investigators will submit detailed findings from the primary analysis for presentation at a future international scientific meeting.

“The positive topline results from WU-KONG28 study represent an important advancement for treating patients with EGFR [exon 20 insertion mutation–positive] NSCLC,” principal trial investigator Caicun Zhou, MD, PhD, a professor from Shanghai East Hospital, said in the press release.¹ “[Sunvozertinib] is currently the only single-agent, small-molecule targeted therapy approved in both China and the US for patients with EGFR exon 20 insertion [mutation–positive] NSCLC. In this phase 3 trial, first-line treatment with [sunvozertinib] significantly prolonged PFS compared to platinum-based doublet chemotherapy. These results suggest that ZEGFROVY may offer an effective and convenient treatment option for treatment-naïve patients with EGFR [exon 20 insertion mutation–positive] NSCLC.”

Investigators of the international phase 3 WU-KONG28 trial evaluated the safety and activity of sunvozertinib across 16 countries and regions in Asia, Europe, North America, and South America. Patients were randomly assigned to receive sunvozertinib at 300 mg orally once daily or 6 cycles of pemetrexed at 500 mg/m² plus carboplatin area under the curve 5 intravenously every 3 weeks.² In the chemotherapy arm, patients whose disease did not progress following 4 cycles of frontline platinum-containing chemotherapy were eligible to receive pemetrexed maintenance therapy.

The trial’s primary end point was PFS per blinded independent central review using RECIST v1.1 criteria. Overall survival was a secondary end point measured for up to approximately 34 months after random assignment.

Patients 18 years and older with histologically or cytologically confirmed nonsquamous, locally advanced, or metastatic NSCLC not suitable for curative treatment and availability of adequate tumor tissue were eligible for enrollment on the trial. Other eligibility criteria included having at least 1 measurable lesion based on RECIST v1.1 guidelines, a minimum life expectancy of 12 weeks, an ECOG performance status of 0 or 1, and adequate organ and hematologic function.

Those with prior systemic therapy for locally advanced or metastatic NSCLC, spinal cord compression or leptomeningeal metastasis, or a history of stroke or intracranial hemorrhage within 6 months of random assignment were ineligible for enrollment on the trial. Having concurrent EGFR mutations such as exon 19 deletions, L858R, T790M, G719X, S768I, L861Q was also grounds for exclusion.

“Finding a drug targeting EGFR exon 20 insertion mutations is especially challenging due to their enormous heterogeneity. We have identified over 100 different subtypes of EGFR [exon 20 insertion mutations] clinically. Despite tremendous efforts, there is no success yet in finding an effective target drug that can spare patients from chemotherapies. WU-KONG28 study has the potential to change all that,” Xiaolin Zhang, PhD, chief executive officer at Dizal, the developer of sunvozertinib, stated in the press release.¹ “The success of this multinational pivotal study further validates [sunvozertinib’s] potential as first-line therapy for patients with EGFR [exon 20 insertion mutation–positive] NSCLC.”

References

1. Dizal announces positive topline phase 3 results from WU-KONG28 study: evaluating oral, once-daily ZEGFROVY® (Sunvozertinib) vs. platinum-containing chemo doublet in first-line non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). News release. Dizal. March 21, 2026. Accessed March 23, 2026. https://tinyurl.com/3jt78uvp
2. A study of DZD9008 versus platinum-based doublet chemotherapy in local advanced or metastatic non-small cell lung cancer (WU-KONG28). ClinicalTrials.gov. Updated February 17, 2026. Accessed March 23, 2026. https://tinyurl.com/mr8df7ay